Key pathways involved in prostate cancer based on gene set ... · The major challenge for genome-wide RNA expression analysis is not to obtain gene expression profiles, but to extract

©FUNPEC-RP www.funpecrp.com.brGenetics and Molecular Research 10 (4): 3856-3887 (2011)

Key pathways involved in prostate cancer based on gene set enrichment analysis and meta analysis

Q.Y. Ning1, J.Z. Wu1, N. Zang2, J. Liang3, Y.L. Hu2 and Z.N. Mo4

1Department of Infection, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China2The Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China3Department of Biology Technology, Guilin Medical University,Guilin, Guangxi Zhuang Autonomous Region, China4Department of Urology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China

Corresponding authors: Y.L. Hu / Z.N. MoE-mail: [email protected] / [email protected]

Genet. Mol. Res. 10 (4): 3856-3887 (2011)Received June 7, 2011Accepted October 14, 2011Published December 14, 2011DOI http://dx.doi.org/10.4238/2011.December.14.10

ABSTRACT. Prostate cancer is one of the most common male malignant neoplasms; however, its causes are not completely understood. A few recent studies have used gene expression profiling of prostate cancer to identify differentially expressed genes and possible relevant pathways. However, few studies have examined the genetic mechanics of prostate cancer at the pathway level to search for such pathways. We used gene set enrichment analysis and a meta-analysis of six independent studies after standardized microarray preprocessing, which increased concordance between these gene datasets. Based on gene set enrichment analysis, there were 12 down- and 25 up-regulated mixing pathways in more than two tissue datasets, while there were two down- and two up-regulated mixing pathways in three cell datasets. Based on the meta-analysis, there were 46 and nine common pathways in the tissue and cell datasets, respectively. Three up- and 10 down-regulated crossing pathways were


Q.Y. Ning et al. 3856

detected with combined gene set enrichment analysis and meta-analysis. We found that genes with small changes are difficult to detect by classic univariate statistics; they can more easily be identified by pathway analysis. After standardized microarray preprocessing, we applied gene set enrichment analysis and a meta-analysis to increase the concordance in identifying biological mechanisms involved in prostate cancer. The gene pathways that we identified could provide insight concerning the development of prostate cancer.

Key words: Prostate cancer; Gene set enrichment analysis;Meta-analysis

INTRODUCTION

Prostate cancer (PC) is one of the most common male malignant neoplasms in the world, and its incidence has increased year by year in China (Liang et al., 2007). Although large-scaled studies have been involved in prostate cancer, the mechanism involved still re-mained completely unclear until now. In order to reveal this mystery, a few recently reported studies have been developed using gene expression profiling of PC to identify differentially expressed genes from several to hundreds (Endo et al., 2009; Nadiminty et al., 2010), but these studies only focused on the individual gene. Prostate cancer is a complex disease and involves a number of gene interactions. Singling out and explaining individual genes on a list with a thousand important genes is still very difficult.

The major challenge for genome-wide RNA expression analysis is not to obtain gene expression profiles, but to extract a biological insight from the results (Subramanian et al., 2005). Of course, genome-wide expression analysis with DNA microarray have been used to identify predefined biological pathways associated with the phenotypic variations for many researches (Nanni et al., 2006; Chandran et al., 2007; Wallace et al., 2008). However, the con-firmed biological pathways from these methods only represent a very small part of the entire range of pathways involved in prostate cancer.

To resolve this conflict, Mootha et al. (2003) described a method-Gene Set Enrich-ment Analysis (GSEA) which has been recognized as the most well-known and effective ap-proach to gene set analysis. These authors have used it to identify predefined gene sets which showed significant differences in expression between normal and patient’s samples. Subse-quently, Subramanian et al. (2005) improved the methodology and specifically introduced the method of how to use GSEA.

GSEA which is based on the predefined sets of genes that usually derived from func-tional annotation or from results of prior experiments, can identify more subtle changes of gene expression, because the biggest advantage of GSEA is that the statistical results are ob-tained from groups or pathways rather than individual gene. Over the years, GSEA had been gradually applied to some areas (Suarez-Farinas et al., 2010 ). In addition, meta-analysis as a standard statistical method has become more widespread and has been applied in many fields. In this study, after a standardized microarray preprocessing for all the expression datasets, GSEA and a meta analysis were used to find the mixing pathways which provided a systematic insight into the pathways that changed during the mechanism of PC.


Key pathways involved in prostate cancer 3857

MATERIAL AND METHODS

Datasets

The gene expression profiling studies about prostate cancer were searched from GEO (http://www.ncbi.nlm.nih.gov/geo/), and ArrayExpress (http://www.ebi.ac.uk/ arrayexpress/). Any data that met the following conditions was selected for inclusion: 1) the data was about genome-wide RNA expression; 2) the complete microarray raw or normalized data was effec-tive; 3) the data provided a comparison between prostate cancer patients and controls; 4) Three or more samples were contained in the data.

Finally, we found five gene expression datasets which met the above criteria. In da-taset GSE3868, two samples were removed because they were human prostate hyperplasia primary samples, and the other twenty-eight samples were all included in the processing. In dataset GSE6919 with U95 Version 2, 25 patients with metastatic prostate tumor samples in paratracheal lymph node and 63 patients with normal prostate tissue adjacent to the tumor were not included in the research. We summarized all the detailed information about the data-sets, such as the first author or contributor, microarray platform, sample type, sample size, and they are shown in Table 1.

First author or contributor Chip GEO Experimental Classification Probs Number of accession design samples

Disease Normal

Yegnasubramanian S U133 A GSE12348 unpaired, cells prostate cancer 22K 6 3 (Yegnasubramanian et al., 2008)Wallace TA U133A 2.0 GSE6956 unpaired, tissues prostate cancer 22K 69 20 (Wallace et al., 2008)Nanni S (Nanni et al., 2006) U133A GSE3868 unpaired, cells prostate cancer 22K 23 5Chandran UR (Yu et al., 2004; U95 Version 2 GSE6919 unpaired tissues Prostate tumor 12K 65 18 Chandran et al., 2007)Vellaichamy A U133 Plus 2.0 GSE17044 unpaired, cells prostate cancer cells 54K 3 3 (Vellaichamy et al., 2009)

Paried = compare prostate cancer to normal controls from the same patients with prostate cancer; Unparied = compare prostate cancer from men with prostate cancer to normal controls from men without prostate cancer; cells = human prostate cancer cells samples.

Table 1. Characteristics of datasets selected in the studies.

Data processing of standardized microarray preprocessing

Software packages developed in version 2.10.1 of Bioconductor (Mootha et al., 2003) were applied for data preprocessing. The Robust Multichip Averaging (RMA) algorithm in the affy conductor package was used for each affymetrix raw dataset to calculate background adjusted, normalized and log2 probe-set intensities. The affy U133A normalizations shown in GSE3868 was also retained for further analysis. We selected genes which could be mapped to any explicit KEGG pathway for the further analysis of GSEA and meta-analysis. The measure of variability was within the interquartile range (IQR) and a cut-off was set up to remove IQR values under 0.5 for all the remaining genes. If one gene was targeted for multiple probe sets, we retained the probe set with the largest variability. Pathway analysis of each dataset was performed independently.



Data processing of GSEA

GSEA performed using the Category version 2.10.1 package (Mootha et al., 2003). The gene sets represented by more than 10 genes were retained. The Student’s-t-test statistical score was implemented in each pathway and the mean of the genes was calculated. A permuta-tion test with 1000 times was used to identify the significantly changed pathways and p-value was less than or equaled to 0.05.

Data processing of meta-analysis

To obtain the common gene sets for the datasets regarding prostate tissues or cells independently from the above remaining genes of each dataset, we then calculated the chi-square value of each gene based on the formula according to Brown (1975):

and a cut-off was also set up to remove chi-square values under 0.05 for all the surplus genes which were used to obtain the pathways of the KEGG from DAVID Bioinformatics Resources 6.7 (http://david.abcc.ncifcrf.gov/). K is the number of datasets.

RESULTS

Re-analyzing each dataset to produce differentially expressed pathways

The five inclusion datasets contain 166 prostate cancer cases and 49 controls. All the datasets were implemented with a common GSEA method. For each separate analysis, the sig-nificant pathways and the genes were also obtained with GSEA and the detailed information about the analysis results are shown in Table 2.

In our studies, experimental design of 2 datasets (Chandran et al., 2007; Wallace, 2008) was related to prostate cancer tissues, while the other three datasets (Nanni et al., 2006; Yegnasubramanian et al., 2008; Vellaichamy et al., 2009) were related to prostate cancer cells. Finally, we found that the consistent pathways were separate in tissue and cell from GSEA and the meta-analysis result.

Studies Number of Number of Number of genes Number of pathways Up-regulated Down-regulated patients controls after pre-processing have genes >10 pathways pathways

GSE17044 3 3 2421 219 0 0GSE12348 6 3 2184 217 38 30GSE3868 23 5 3814 216 6 17GSE6956 69 20 2214 214 93 10GSE6919 U95 Version 2 65 18 1810 213 72 1

Table 2. Summary of each dataset used in the re-analysis and the number of differentially expressed pathways in gene set enrichment analysis (GSEA).



Common significant pathways obtained from two prostate cancer tissue datasets by GSEA

There were 1 up and 53 down-regulated pathways that existed in 2 prostate cancer tissues datasets, the details can be seen in Additional Table 1. The up-regulated pathway con-cerned genetic information processing and translation. Most of the representative pathways in down-regulated pathways were associated with metabolism, biosynthesis, signal transduction, cell communication and organismal systems.

Common significant pathways obtained from three prostate cancer cell datasets by GSEA

Except for prostate cancer tissues, datasets regarding prostate cancer cells were also added to our studies. For single datasets analysis, there was no up or down-regulated pathway detected in GSE17044. The reason may be that there was only a limited number of samples available. There were 38 up- and 30 down-regulatory pathways in GSE12348, and 6 and 17 in GSE3868. Also, there were four mixing pathways including 2 up and 2 down-regulated pathways from these 2 datasets. The details are shown in Additional Table 2.

Common significant pathways obtained from these prostate cancer datasets by meta-analysis

To further identify the results, we obtained common significant pathways and genes from these datasets by meta-analysis. In total, there were 1905 significant genes and 39 com-mon pathways in two tissues datasets. Most of these pathways concernedCancers, Cardiovas-cular Diseases, Cell Communication, Signal Transduction, Cellular Processes, Environmental Information Processing, Human Diseases and Organismal Systems. The details are shown in Additional Table 3. Otherwise, 131 significant genes and 9 common pathways were identified in the three cell datasets. The main pathways concerned Lipid Metabolism and Amino Acid Metabolism. The results are shown in Additional Table 4.

Common crossing significant pathways between the results of GSEA andmeta-analysis

To search the intersection pathways, a comparative analysis was made independently between the common significant pathways of GSEA and meta-analysis in cancer tissues or cells. Finally, 15 consistent pathways were obtained in tissue datasets and the details are shown in Additional Table 5. In this table, the pathways were primarily concerned metabolism, en-vironmental information processing, signal transduction, signaling molecules and interaction, human diseases, cancers. However, no consistent pathways were detected in cell datasets.

mRNA expression in human prostate cancers tissue

In order to improve the above results, we searched for a dataset which was able to show the experience according to prostate carcinoma vs normal tissue using the publically



available ONCOMINE cancer gene expression microarray database (Singh et al., 2002). The platform for this dataset is U95Av2 arrays (Affymetrix). The sample included 50 normal and 52 tumor prostate tissues. The raw data was downloaded from (http://www.broadinstitute.org/cgi-bin/cancer/publications/pub_paper.cgi?mode=view&paper_id=75). We also used the same GSEA program to enrich the pathways. Finally, we enriched 27 up-regulated and 66 down-regulated pathways. The results are shown in Additional Table 6. Except for two path-ways, which is glycolysis/gluconeogenesis, starch and sucrose metabolism, the other 13 path-ways as shown in Additional Table 5 were included in these enriched pathways.

DISCUSSION

PC is one of the most serious diseases and its mechanism still remains completely unclear. No single theory can provide a perfect definition for all the different cases of prostate cancer. The genome-wide microarrays can locate gene families and pathways which show a consistent alteration in a disease state. Pathway analysis is a valid method to reduce a major deviation and can obtain interesting common genes and pathways by mixing differently ex-pressed genes from different datasets. Therefore, we can apply the pathway analysis to search for genes which are difficult to detect by univariate statistical analysis because of their subtle change. Gene set enrichment analysis and a meta-analysis were applied to five datasets to extract biological insights involved in prostate cancer. Our findings suggest that most of the pathways and genes that affect prostate cancer were accordant. In our study, according to functional classification, we discussed several differentially expressed pathways and genes among crossing pathways as shown in Additional Table 5 and which suggest the role of these pathways and genes in prostate cancer.

Environmental information processing

Environmental information processing includes membrane transport, signal transduc-tion, signaling molecules and interaction etc. In our findings, signal transduction, signaling molecules and interaction are common functions in positive pathways. Signal transduction is related to cell proliferation, differentiation and apoptosis. Because most of the signaling molecules and interaction are involved in the processing of signal transduction, signaling mol-ecules and interaction connect closely with signal transduction and may play an important role in the course of prostate cancer. Currently, numerous studies have been applied to explore signal transduction to understand the biological mechanism of prostate cancer (Skvortsova et al., 2008; Aalinkeel et al., 2010). The mitogen-activated protein kinase (MAPK) signal-ing pathway in our studies which belongs to signal transduction is related to various cellular functions. The MAPK cascade is a highly conserved module that is involved in various cel-lular functions, including cell proliferation, differentiation and migration (Takeda and Ichijo, 2002). A number of genes expression in this pathway have been reported to be related with prostate cancer i.e. CD14(+) cells exhibiting reduced expression of HLA-DR molecules in PCa patients. These cells suppress immune cell function in vitro and, therefore, immuno-therapy protocols for PCa patients must be factored into the design (Vuk-Pavlovic et al., 2010). MYC oncogene overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells (Iwata et al., 2010). Overexpression of NF-kappaB2/p52



enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic abil-ity in androgen-deprived condition in vitro. NF-kappaB2/p52 induced androgen-independent growth occurs via protecting LNCaP cells from apoptotic cell death and cell cycle arrest in-duced by androgen-deprivation. Adenoviral mediated NF-kappaB2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-kappaB2/p52 induces androgen-inde-pendent growth of androgen-sensitive LNCaP cells (Nadiminty et al., 2008). CD44+ cells pos-sess stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they have shown a strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay (Lee et al., 2011).

Cellular processes and cell communication

Except for signal transduction and signaling molecules and interaction, cellular pro-cesses and cell communication are also a way of obtaining information transmission between cells. Many junctions among cells are the structural characteristics of smooth muscle and become a channel connected cytoplasm in order to transmit cellular information. Numerous recent studies suggest that the disruption of cell-cell adhesion may be a key mechanism as-sociated with calcitonin (CT)-stimulated prostate cancer progression and metastasis (Shah et al., 2008). Gap junction has been considered to be an important part of junctional com-munication in the prostate morphogenesis and oncogenesis (Mitra et al., 2006) and may also play a pivotal role in invasion and migration of prostate cancer cells (Tate et al., 2006). The idea that focal adhesion is related to cell movement suggests focal adhesion which may be involved in the development and metastasis of tumors. Recent studies have tested the hypoth-esis (Franzen et al., 2009). Epithelial tight junctions are composed of at least three types of transmembrane protein. The transmembrane proteins mediate cell adhesion and are thought to constitute the intramembrane and paracellular diffusion barriers (Balda and Matter, 2003). Cell growth, reproduction, differentiation and apoptosis are involved in signal transduction of cell transmembrane. Therefore, the factors which affect signal transduction of cell transmem-brane will possibly interrupt the function of normal cells. The actin cytoskeleton participates in many fundamental processes including the regulation of cell shape, motility, and adhesion. The remodeling of the actin cytoskeleton is dependent on actin binding proteins, which or-ganize actin filaments into specific structures that allow them to perform various specialized functions (Revenu et al., 2004). Therefore, cell communication may be a possible significant factor for an insight into the biological mechanism of prostate cancer.

Metabolism pathways

The metabolism pathways in our study were mainly focused on lipid metabolism, amino acid metabolism and xenobiotics biodegradation and metabolism. It has been recently confirmed that genes and proteins involved in cellular metabolism play a crucial part in the development and progression of PC (Pettazzoni et al., 2011; Ouyang et al., 2011). Glycoly-sis/Gluconeogenesis pathway belongs to the lipid metabolism. Glycolysis is the process of converting glucose into pyruvate and generating small amounts of adenosine-5’-triphosphate (energy) and nicotinamide adenine dinucleotide. It can produce important precursor metabo-



lites. The gene PGK1 in this pathway has been reported to be significantly differentially ex-pressed between laser microdissected malignant versus benign clinical samples of prostate tissue (Romanuik et al., 2009). Uridine diphosphate (UDP)-glucose dehydrogenase (UGDH) in the amino acid metabolism pathway was found to be significantly differentially expressed in our analysis, and can also catalyze the oxidation of UDP-glucose to yield UDP-glucuronic acid which is a precursor for synthesis of glycosaminoglycans and proteoglycans that promote aggressive PC progression (Huang et al., 2010). Drug metabolism - cytochromes P450 was also observed in our search for pathways. The cytochromes P450 (CYPs) are key enzymes in cancer formation and cancer treatment. They mediate the metabolic activation of numerous precarcinogens and participate in the inactivation and activation of anticancer drugs. There-fore, this pathway may have a relationship with the mechanism of resistance to chemotherapy drugs in prostate cancer. In the finding genes of this pathway, CYP3A4 and CYP3A5 expres-sion is related to androgen metabolism (Rebbeck et al., 2008). Meta-analysis studies show that measurement of GSTP1 promoter methylation in plasma, serum, or urine samples may complement PSA screening for prostate cancer diagnosis (Wu et al., 2011).

Endocrine system

The insulin signaling pathway in our study belongs to both the organismal and en-docrine systems. Most of the positive genes in this pathway have been reported to be related to prostate cancer. Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase. Signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF, and MEK that lead to activation of MAPK and mitogenic response in the form of gene transcription. FASN can act as a prostate cancer oncogene in the presence of AR and then FASN exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis (Migita e t al., 2009). Expression of p66(Shc) protein correlates with proliferation of human prostate cancer cells (Veeramani et al., 2005). Increasing mTOR activity and protein synthesis did not translate into enhanced cell proliferation rates. However, the lack of TSC2 resulted in a sur-vival advantage when cells were exposed to hypoxia. Protection against hypoxia-induced cell death due to TSC2 deficiency is rapamycin-resistant, suggesting that TSC2 affects an apop-totic pathway. Tumors derived from TSC2 wild-type cells exhibited a growth delay compared with TSC2-deficient tumors, indicating that enhancing mTOR activity is advantageous in the initial phase of tumor growth (Kaper et al., 2006).

Other pathways and genes

As shown in Additional Table 3, except for the above pathways, the remaining path-ways all belong to the classification of human diseases and cancers. Most of genes in these pathways can be enriched in the above pathways. Smad3 in chronic myeloid leukemia path-way is an important gene for prostate cancer and this has widely been reported in the litera-ture. Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-beta responses, including control of gene expression, cell growth, apoptosis, and tumor suppression (Yang et al., 2009). Deregulated/enhanced expression and activation of AR in prostate carci-nomas may intercept the tumor suppressor function of TGF-β through transcriptional suppres-



sion of Smad3 (Song et al., 2010).

CONCLUSION

The pathogenesis of PC is quite complicated. We were able to gain an insight into the mechanisms by focusing on gene sets or pathways rather than on individual genes. In our research, many consistent biological mechanisms involved in PC were identified by GSEA and meta-analysis after a standardized microarray preprocessing, which were original in terms of their connection to PC (as obtained from the current literature). In addition, the enriched pathways can be improved by a tissue dataset from the Oncomine database. Further studies about the specific role and interactions of the genes included in related pathways are needed to improve the understanding of prostate cancer.

ACKNOWLEDGMENTS

In this research, we had a great amount of help. During writing and running the pro-gram, Zhao Hongbo, Zhang Jiange, etc., provided substantial assistance. Research supported by the National Natural Science Foundation of China (grant #81060213), Guangxi Natural Science Foundation (Grant #2011GXNSFB018100).

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SUPPLEMENTARY MATERIAL

Pathway Pathway names Classification P value Number of genes Included genes expressed in the pathways

03010 Ribosome Genetic information 0.01 36 RPL23P6, RPL27A, RPL29P11, RPL29P12, processing and RPL29P26, RPL29P9, RPL31P17, RPL31P49, translation RPL38, RPL5P1, RPL5P34, RPS11P5, RPS19P3, RPS28, RPS28P6, RPS28P9, RPS2P11, RPS2P12, RPS2P17, RPS2P20, RPS2P5, RPS2P51, RPS2P55, RPS2P8, RPl27, RPl14, RPl23, RPl28, RPl29, RPl31, RPl5, RPS11, RPS 19, RPS 2, RPS 20, RPS 21

Additional Table 1. Common significant pathways obtained from 2 prostate cancer tissue datasets by GSEA up-regulated pathways.

Pathway Pathway names Classification P value Number of genes Included genesentry expressed in the pathways

00260 Glycine, serine and Amino acid 0.008 11 C8orf62; Gamt; MAOA; PHGDH; PSAT1; threonine metabolism metabolism PSPH; PSPHL; SHMT2; dld; gcat; srr04120 Ubiquitin mediated sorting and 0.008 65 ANAPC5; CUL5; CUL7; Fbxo2; Fbxw11; proteolysis degradation HERC2; HUWE1; ITCH; KLHL9; LOC100132973; LOC730429; NEDD4; PIAS1; PIAS2; RBX1; SAE1; SMURF1; SMURF2; STUB1; TCEB1; Tceb2; Trip12; UBA2; UBA6; UBE2A; UBE2C; UBE2D3P; UBE2E1; UBE2G2; UBE2I; UBE2J1; UBE2MP1; UBE2N; UBE3B; UBE3C; UBR5; Uba1; Uba7; Ube2e3; Ube2h; Ube2l6; Ube2m; Ube2q1; Ube2s; Ube3a; Ube4b; WWP1; WWP2; btrc; cul3; cul4a; erc4; keap1; grn1; prpf19; rnf7; trim32; uba3; ube2b; ube2d2; ube2d3; ube2d4; ube2g1; ube2l3; ube4a

Additional Table 2. Common significant pathways obtained from 3 prostate cancer cell datasets by GSEA up-regulated pathways.


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orm

atio

n 1.

63E-

07

59

TLN

1, P

TEN

, AK

T1, A

CTG

1, C

DC

42, P

AK

3, P

AK

4, IL

K, S

HC

1, Z

YX

,

Pr

oces

sing

; Sig

nal T

rans

duct

ion

PIK

3CG

, RO

CK

2, A

CTN

1, F

LNC

, FLN

A, P

PP1C

A, C

CN

D1,

CC

ND

2, JU

N,

M

APK

3, P

DG

FRA

, MY

L7, C

AV2,

CAV

1, G

RB

2, T

NC

, ITG

B4,

ITG

B3,

IT

GB

1, L

AM

B4,

PTK

2, R

AC

3, IT

GB

8, B

CL2

, SO

S2, C

OL6

A2,

CO

L6A

1,

PIK

3R3,

TH

BS1

, TH

BS3

, FN

1, A

CTB

, CO

L4A

2, F

LT1,

CO

L4A

1, T

NX

A,

M

ET, R

AF1

, HG

F, K

DR

, VW

F, L

AM

A4,

ITG

A6,

ITG

A5,

LA

MA

5, IT

GA

7,

RA

P1A

, CR

K, M

YLK

0522

0 Ch

roni

c m

yelo

id

Chro

nic

mye

loid

leuk

emia

3.

65E-

04

24

PIK

3CG

, CTB

P2, B

CR, G

RB2,

MA

P2K

2, T

GFB

R2, T

GFB

3, S

MA

D3,

RA

F1,

le

ukem

ia

PT

PN11

, AK

T1, C

CND

1, H

DA

C1, S

OS2

, MA

PK3,

MD

M2,

SH

C1, A

BL1,

PI

K3R

3, R

UN

X1,

IKBK

B, C

RK

, MY

C, C

HU

K

0452

0 A

dher

ens j

unct

ion

Cel

lula

r Pro

cess

es; C

ell

5.55

E-04

24

A

CTB

, PTP

RB

, PA

RD

3, P

TPR

F, B

AIA

P2, M

ET, T

GFB

R2,

SM

AD

3, L

EF1,

Com

mun

icat

ion

AC

TN1,

CTN

ND

1, C

DH

1, S

NA

I2, C

TNN

A1,

IQG

AP1

, FA

RP2

, AC

TG1,

C

DC

42, T

JP1,

CSN

K2A

1, R

AC

3, P

VR

L2, M

APK

3, S

SX2I

P

0451

2 EC

M-re

cept

or

Envi

ronm

enta

l Inf

orm

atio

n 8.

63E-

04

25

TNC

, ITG

B4,

ITG

B3,

ITG

B1,

SD

C2,

LA

MB

4, G

P5, C

D44

, ITG

B8,

CO

L6A

2,

inte

ract

ion

Proc

essi

ng; S

igna

ling

CO

L6A

1, S

V2A

, AG

RN

, TH

BS1

, TH

BS3

, FN

1, C

OL4

A2,

CO

L4A

1, T

NX

A,

Mol

ecul

es a

nd In

tera

ctio

n

V

WF,

LA

MA

4, IT

GA

6, IT

GA

5, L

AM

A5,

ITG

A7

0541

2 A

rrhy

thm

ogen

ic

Envi

ronm

enta

l Inf

orm

atio

n 0.

0011

58

23

AC

TB, I

TGB

4, C

AC

NB

1, L

EF1,

AC

TN1,

GJA

1, IT

GB

3, C

TNN

A1,

ITG

B1,

rig

ht v

entri

cula

r Pr

oces

sing

; Sig

nalin

g

JU

P, A

CTG

1, D

ES, S

GC

G, A

TP2A

2, IT

GA

6, IT

GA

5, IT

GB

8, D

MD

, ITG

A7,

ca

rdio

myo

path

y M

olec

ules

and

Inte

ract

ion

DSP

, CA

CN

A1D

, SG

CA

, SG

CB

(A

RVC

)

0304

0 Sp

liceo

som

e Sp

liceo

som

e 0.

0012

38

33

CH

ERP,

U2A

F2, L

SM6,

TR

A2A

, SN

RPB

2, S

R14

0, S

ART

1, H

NR

NPA

3,

TCER

G1,

HN

RN

PK, S

FRS5

, DH

X38

, DD

X23

, HSP

A2,

PR

PF8,

PC

BP1

,

LSM

3, S

NR

NP7

0, A

CIN

1, R

BM

25, P

RPF

40A

, BC

AS2

, SN

RPA

1, S

FRS1

,

DD

X5,

PRP

F4, H

NRN

PA1,

SFR

S3, H

NRN

PU, S

NRP

A, P

UF6

0, S

NRP

G, B

AT1

0521

0 C

olor

ecta

l can

cer

Envi

ronm

enta

l Inf

orm

atio

n 0.

0020

51

24

PIK

3CG

, DV

L3, M

SH3,

GR

B2,

CY

CS,

TG

FBR

2, M

ET, T

GFB

3, S

MA

D3,

Proc

essi

ng; S

igna

ling

Mol

ecul

es

LEF1

, RA

F1, D

VL1

, AK

T1, F

OS,

CC

ND

1, R

AC

3, JU

N, B

CL2

, SO

S2,

and

Inte

ract

ion

MA

PK3,

PD

GFR

A, P

IK3R

3, M

YC

, AX

IN1

0521

3 En

dom

etria

l can

cer

Envi

ronm

enta

l Inf

orm

atio

n 0.

0026

83

17

PIK

3CG

, MA

P2K

2, G

RB

2, L

EF1,

RA

F1, C

DH

1, F

OX

O3,

CTN

NA

1, P

TEN

,

Pr

oces

sing

; Sig

nalin

g M

olec

ules

A

KT1

, CC

ND

1, IL

K, M

APK

3, S

OS2

, PIK

3R3,

MY

C, A

XIN

1

an

d In

tera

ctio

n

0522

1 A

cute

mye

loid

H

uman

Dise

ases

; Can

cers

0.

0035

4 18

PI

K3C

G, M

AP2

K2,

GR

B2,

PM

L, L

EF1,

RA

F1, S

TAT3

, AK

T1, J

UP,

CC

ND

1,

leuk

emia

SOS2

, MA

PK3,

RA

RA

, RU

NX

1, IK

BK

B, P

IK3R

3, M

YC

, CH

UK

0472

2 N

euro

troph

in

Org

anis

mal

Sys

tem

s;

0.00

3847

31

G

RB

2, F

OX

O3,

MA

GED

1, A

KT1

, CD

C42

, BC

L2, S

OS2

, GA

B1,

SH

C1,

si

gnal

ing

path

way

N

ervo

us S

yste

m

CA

MK

2B, S

H2B

1, C

SK, P

IK3R

3, A

RH

GD

IA, P

IK3C

G, N

TF3,

MA

P2K

2,

RA

F1, P

RK

CD

, IR

S1, P

TPN

11, A

TF4,

RPS

6KA

1, JU

N, M

APK

3, R

AP1

A,

A

BL1

, IK

BK

B, C

RK

, CA

LM1,

NG

F

Add

ition

al T

able

3. C

omm

on si

gnifi

cant

pat

hway

s obt

aine

d fr

om 2

pro

stat

e ca

ncer

tiss

ue d

atas

ets b

y m

eta-

anal

ysis

.

Con

tinue

d on

nex

t pag

e


Key pathways involved in prostate cancer 3867Pa

thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

e ge

nes

entry

expr

esse

d in

the

path

way

s

0521

1 Re

nal c

ell c

arci

nom

a En

viro

nmen

tal I

nfor

mat

ion

0.00

5404

20

PI

K3C

G, M

AP2

K2,

GRB

2, M

ET, T

GFB

3, R

AF1

, HG

F, A

RNT,

PTP

N11

, AK

T1,

Proc

essi

ng; S

igna

ling

Mol

ecul

es

CDC4

2, P

AK

3, JU

N, P

AK

4, G

AB1

, SO

S2, M

APK

3, R

AP1

A, P

IK3R

3, C

RK

an

d In

tera

ctio

n

0481

0 R

egul

atio

n of

act

in

Org

anis

mal

Sys

tem

s;

0.00

5587

47

M

YL7

, FG

F7, M

RA

S, IT

GA

E, IT

GB

4, IQ

GA

P2, R

DX

, FG

F12,

ITG

B3,

cy

tosk

elet

on

Dev

elop

men

t

PI

P5K

1A, G

NG

12, I

TGB

1, IQ

GA

P1, A

CTG

1, C

DC

42, P

TK2,

EZR

, ITG

B8,

G

SN, R

AC3

, PA

K3,

PA

K4,

SO

S2, M

SN, P

IK3R

3, C

SK, F

GF2

, FN

1, P

IK3C

G,

A

CTB,

RO

CK2,

MA

P2K

2, B

AIA

P2, R

AF1

, ACT

N1,

MY

H9,

PPP

1CA

, ITG

A6,

IT

GA

5, R

RAS2

, MA

PK3,

ITG

A7,

PD

GFR

A, C

RK, M

YLK

, CD

14, F

2R

0453

0 Ti

ght j

unct

ion

Envi

ronm

enta

l Inf

orm

atio

n 0.

0067

53

32

MY

L7, C

LDN

7, P

AR

D3,

OC

LN, G

NA

I2, C

LDN

4, C

LDN

3, M

RA

S, C

LDN

5,

Pr

oces

sing

; Sig

nalin

g M

olec

ules

CA

SK, P

TEN

, LLG

L2, A

CTG

1, A

KT1

, CD

C42,

CTT

N, C

SNK

2A1,

PPP

2CB,

and

Inte

ract

ion

ACT

B, P

PP2R

1A, S

YM

PK, P

ARD

6B, I

NA

DL,

ACT

N1,

MY

H9,

CSD

A, C

TNN

A1,

PR

KCD

, TJP

1, E

PB41

L1, R

RAS2

, JA

M3

0513

0 Pa

thog

enic

M

etab

olism

; Bio

synt

hesis

of

0.00

7283

17

A

CTB,

ARH

GEF

2, O

CLN

, RO

CK2,

TU

BB2C

, CD

H1,

ITG

B1, A

CTG

1, C

DC4

2,

Esch

eric

hia

coli

Oth

er S

econ

dary

Met

abol

ites

CTTN

, EZR

, KRT

18, T

UBA

3C, T

UBA

4A, T

UBA

1A, A

BL1,

CD

14

infe

ctio

n

0491

0 In

sulin

sign

alin

g H

uman

Dis

ease

s;

0.00

756

32

PHK

A2,

GR

B2,

RH

OQ

, PD

E3B

, AK

T1, P

PP1R

3C, S

OS2

, FA

SN, G

YS1

,

path

way

In

fect

ious

Dis

ease

s

G

YS2

, SH

C1,

PR

KA

A1,

PIK

3R3,

SR

EBF1

, PIK

3CG

, PTP

RF,

PH

KG

1,

MA

P2K

2, P

RK

AB

2, A

CA

CA

, FB

P1, R

AF1

, IR

S1, P

PP1C

A, P

YG

M, P

YG

L,

MA

PK3,

TSC

2, R

HEB

, IK

BK

B, C

RK

, CA

LM1

0522

2 Sm

all c

ell l

ung

Hum

an D

isea

ses;

Can

cers

0.

0097

91

22

PIK

3CG

, CK

S1B

, FH

IT, C

OL4

A2,

CO

L4A

1, C

YC

S, IT

GB

1, P

TEN

, AK

T1,

ca

ncer

LAM

B4, P

TK2,

CCN

D1,

LA

MA

4, IT

GA

6, L

AM

A5,

BCL

2, IK

BKB,

PIK

3R3,

M

YC,

CH

UK

, TRA

F4, F

N1

0520

0 Pa

thw

ays i

n ca

ncer

M

etab

olism

; Met

abol

ism

0.01

1061

65

FG

F7, T

GFB

3, F

GF1

2, N

FKB

2, P

TEN

, AK

T1, C

DC

42, F

OS,

RA

RA

, WN

T6,

of C

ofac

tors

and

Vita

min

s

TP

R, M

YC

, FG

F2, C

HU

K, P

IK3C

G, P

LD1,

CTB

P2, B

CR

, CY

CS,

LEF

1,

CTN

NA

1, D

APK

1, JU

P, C

CN

D1,

JUN

, MA

PK3,

PD

GFR

A, M

DM

2, G

STP1

,

KS1

B, G

RB

2, P

ML,

CD

H1,

ITG

B1,

AR

NT,

LA

MB

4, P

TK2,

RA

C3,

BC

L2,

SO

S2, P

IK3R

3, R

UN

X1,

TR

AF4

, AX

IN1,

FN

1, D

VL3

, CO

L4A

2, C

OL4

A1,

M

SH3,

KLK

3, M

AP2

K2,

MET

, TG

FBR

2, S

MA

D3,

RA

F1, H

GF,

STA

T3,

D

VL1

, LA

MA

4, H

DA

C1,

ITG

A6,

LA

MA

5, IK

BK

B, A

BL1

, CR

K

0541

0 H

yper

troph

ic

Hum

an D

isea

ses;

0.

0112

4 22

A

CTB

, AC

TC1,

PR

KA

B2,

ITG

B4,

TG

FB3,

CA

CN

B1,

ITG

B3,

TPM

2,

card

iom

yopa

thy

Infe

ctio

us D

isea

ses

ITG

B1,

AC

TG1,

DES

, SG

CG

, ATP

2A2,

ITG

A6,

ITG

A5,

ITG

B8,

DM

D,

(H

CM

)

ITG

A7,

PR

KA

A1,

CA

CN

A1D

, SG

CA

, SG

CB

0541

4 D

ilate

d H

uman

Dis

ease

s;

0.01

412

23

AC

TB, A

CTC

1, A

DC

Y6,

ITG

B4,

TG

FB3,

CA

CN

B1,

ITG

B3,

TPM

2, IT

GB

1,

card

iom

yopa

thy

Infe

ctio

us D

isea

ses

ACT

G1,

DES

, SG

CG, A

TP2A

2, IT

GA

6, IT

GA

5, IT

GB8

, PLN

, DM

D, I

TGA

7,

GN

AS,

CA

CNA

1D, S

GCA

, SG

CB

Add

ition

al T

able

3. C

ontin

ued.

Con

tinue

d on

nex

t pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

e ge

nes

entry

expr

esse

d in

the

path

way

s

0454

0 G

ap ju

nctio

n O

rgan

ism

al S

yste

ms;

0.

0188

37

22

GN

AI2

, MA

P2K

2, G

RB

2, A

DC

Y6,

TU

BB

2C, G

JA1,

RA

F1, L

PAR

1, IT

PR3,

Sens

ory

Syst

em

GRM

1, IT

PR1,

ITPR

2, T

JP1,

CSN

K1D

, SO

S2, M

APK

3, P

DG

FRA

, TU

BA3C

,

TUBA

4A, G

NA

S, T

UBA

1A, H

TR2A

0413

0 SN

AR

E in

tera

ctio

ns

Org

anis

mal

Sys

tem

s;

0.01

9212

12

ST

X6,

STX

8, S

TX4,

STX

12, S

TX2,

STX

16, V

AM

P5, G

OSR

2, V

AM

P3,

in

ves

icul

ar tr

ansp

ort

Ner

vous

Sys

tem

G

OSR

1, V

AM

P2, S

NA

P23

0501

2 Pa

rkin

son’

s dis

ease

O

rgan

ism

al S

yste

ms;

0.

0204

99

29

ND

UFB

3, U

QC

RC

1, N

DU

FB6,

ND

UFB

8, C

OX

7B, U

CH

L1, P

INK

1,

N

ervo

us S

yste

m

ND

UFS

7, N

DU

FS5,

ND

UFS

4, A

TP5O

, ND

UFS

2, A

TP5J

, CO

X7A

1,

SLC

25A

4, S

LC25

A6,

ND

UFA

6, C

YC

S, V

DA

C2,

UB

E2L3

, CO

X6C

,

VD

AC

1, S

DH

B, U

BA

1, P

PID

, SD

HD

, ATP

5C1,

SLC

18A

2, U

QC

RB

0402

0 C

alci

um si

gnal

ing

Hum

an D

isea

ses;

Can

cers

0.

0259

32

37

PHK

A2,

ER

BB

4, T

NN

C2,

ER

BB

3, E

DN

RA

, AD

RB

3, A

TP2B

3, A

TP2B

4,

path

way

PDE1

C, P

PP3C

B, P

PP3C

C, C

AM

K2B

, PTG

ER3,

SLC

25A

4, P

HK

G1,

SL

C25

A6,

ITPR

3, V

DA

C2,

GR

M1,

ITPR

1, IT

PR2,

VD

AC

1, P

2RX

4,

AD

RB

2, P

LCE1

, ATP

2A2,

PPI

D, P

LN, P

DG

FRA

, AV

PR1A

, TB

XA

2R,

N

AS,

CA

CN

A1D

, MY

LK, C

ALM

1, H

TR2A

, F2R

0001

0 G

lyco

lysis

/

Met

abol

ism; L

ipid

0.

0266

51

16

ALD

OA

, LD

HB

, LD

HA

, PFK

L, A

LDO

B, P

GA

M1,

AD

H5,

FB

P1, A

LDH

3B2,

G

luco

neog

enes

is

Met

abol

ism

AD

H1B

, AD

H1A

, GPI

, ALD

H1B

1, P

GM

1, P

GK

1, G

APD

H, E

NO

1

0401

2 Er

bB si

gnal

ing

Envi

ronm

enta

l Inf

orm

atio

n 0.

0281

42

21

PIK

3CG

, ER

BB

4, E

RB

B3,

MA

P2K

2, G

RB

2, R

AF1

, AK

T1, P

TK2,

PA

K3,

pa

thw

ay

Proc

essi

ng; S

igna

l Tra

nsdu

ctio

n

JU

N, P

AK

4, G

AB

1, S

OS2

, MA

PK3,

SH

C1,

CA

MK

2B, A

BL1

, NR

G1,

PI

K3R

3, C

RK

, MY

C

0521

5 Pr

osta

te c

ance

r H

uman

Dis

ease

s; C

ance

rs

0.03

5202

21

PI

K3C

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LK3,

MA

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2, G

RB

2, L

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RA

F1, P

TEN

, AK

T1, A

TF4,

C

CN

D1,

BC

L2, S

OS2

, MA

PK3,

PD

GFR

A, C

REB

3L1,

MD

M2,

SR

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2,

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KB

, PIK

3R3,

CH

UK

, GST

P1

0050

0 St

arch

and

sucr

ose

Met

abol

ism

; Am

ino

Aci

d 0.

0391

95

12

GPI

, GB

E1, P

YG

M, E

NPP

1, P

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L, P

GM

1, G

AA

, UG

DH

, GY

S1, G

YS2

,

met

abol

ism

M

etab

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m

UG

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1, U

GP2

0407

0 Ph

osph

atid

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l En

viro

nmen

tal I

nfor

mat

ion

0.04

1133

18

PI

K3C

G, I

NPP

1, IN

PPL1

, PI4

KA

, PI4

KB

, PIP

5K1A

, OC

RL,

ITPR

3, C

DS1

,

sign

alin

g sy

stem

Pr

oces

sing

; Sig

nal T

rans

duct

ion

PTEN

, ITP

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ITPR

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LCE1

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KD

, SY

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, IN

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, PIK

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LM1

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cel

l rec

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yste

ms;

0.

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24

18

PIK

3CG

, IFI

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MA

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2, G

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2, R

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, AK

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RA

C3,

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, SO

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si

gnal

ing

path

way

Im

mun

e Sy

stem

A

PK3,

PPP

3CB

, PPP

3CC

, IK

BK

B, P

IK3R

3, N

FATC

3, C

HU

K, B

LNK

0541

6 V

iral m

yoca

rditi

s H

uman

Dis

ease

s;

0.05

4462

17

A

CTB

, CAV

1, C

YC

S, H

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, MY

H9,

CX

AD

R, E

IF4G

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1, C

CN

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Car

diov

ascu

lar D

isea

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, SG

CB

0401

0 M

APK

sign

alin

g En

viro

nmen

tal I

nfor

mat

ion

0.06

3862

50

M

EF2C

, FG

F7, T

GFB

3, F

GF1

2, N

FKB2

, AK

T1, F

OS,

CD

C42,

MY

C, F

GF2

,

path

way

Pr

oces

sing

; Sig

nal T

rans

duct

ion

CHU

K, I

L1A

, FLN

C, F

LNA

, JU

N, R

RAS2

, MA

PK3,

PD

GFR

A, H

SPB1

,

PLA

2G6,

MA

P3K

13, N

GF,

PPP

5C, G

RB2,

MRA

S, C

ACN

B1, G

NG

12,

H

SPA

2, E

LK4,

RA

C3, S

OS2

, JU

ND

, PPP

3CB,

PPP

3CC,

NTF

3, T

AO

K2,

M

AP2

K2,

TG

FBR2

, NF1

, NR4

A1,

RA

F1, A

TF4,

DU

SP3,

DU

SP1,

RPS

6KA

1,

RAP1

A, I

KBK

B, C

RK, C

ACN

A1D

, CD

14

Add

ition

al T

able

3. C

ontin

ued.

Con

tinue

d on

nex

t pag

e



Path

way

Pa

thw

ay n

ames

C

lass

ifica

tion

P va

lue

Num

ber o

f gen

es

Incl

ude

gene

sen

try

ex

pres

sed

in th

e

pa

thw

ays

0467

0 Le

ukoc

yte

Org

anis

mal

Sys

tem

s;

0.06

4448

25

C

LDN

7, M

YL7

, OC

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LDN

4, G

NA

I2, C

LDN

3, C

LDN

5, C

TNN

D1,

tra

nsen

doth

elia

l Im

mun

e Sy

stem

IT

GB

1, A

CTG

1, C

DC

42, P

TK2,

EZR

, CX

CR

4, M

SN, P

IK3R

3, A

CTB

,

mig

ratio

n

PIK

3CG

, RO

CK

2, A

CTN

1, C

TNN

A1,

PTP

N11

, PEC

AM

1, R

AP1

A, J

AM

3

0003

0 Pe

ntos

e ph

osph

ate

Met

abol

ism

; Car

bohy

drat

e 0.

0667

47

8 A

LDO

A, G

PI, P

FKL,

ALD

OB

, PG

M1,

PG

D, F

BP1

, TK

T

path

way

M

etab

olis

m

0098

2 D

rug

met

abol

ism -

M

etab

olism

; Xen

obio

tics

0.06

8111

15

CY

P3A

4, C

YP3

A5,

CY

P3A

7, C

YP2

D6,

AD

H5,

ALD

H3B

2, A

DH

1B, A

DH

1A,

cy

toch

rom

e P4

50

Bio

degr

adat

ion

and

Met

abol

ism

M

GST

3, C

YP2

A13

, FM

O5,

GST

M3,

AO

X1,

UG

T2A

1, G

STO

1, G

STP1

0414

4 En

docy

tosi

s C

ellu

lar P

roce

sses

; 0.

0701

17

36

PAR

D3,

CLT

B, E

RB

B4,

RA

B5B

, RA

B5C

, ER

BB

3, P

IP5K

1A, C

HM

P2B

,

Tr

ansp

ort a

nd C

atab

olis

m

CD

C42

, AD

RB

3, A

P2B

1, H

SPA

2, C

XC

R4,

SH

3GLB

1, R

AB

11A

, NED

D4L

,

AG

AP1

, IQ

SEC

1, S

H3G

L3, P

AR

D6B

, PLD

1, F

LT1,

RA

B4A

, MET

,

TGFB

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PSD

4, H

LA-C

, KD

R, R

AB

31, A

P2A

2, A

DR

B2,

NED

D4,

PD

GFR

A, M

DM

2, D

NM

2, F

2R

0521

4 G

liom

a H

uman

Dis

ease

s; C

ance

rs

0.07

6149

15

PI

K3C

G, M

AP2

K2,

GR

B2,

RA

F1, P

TEN

, AK

T1, C

CN

D1,

MA

PK3,

SO

S2,

PD

GFR

A, M

DM

2, S

HC

1, C

AM

K2B

, PIK

3R3,

CA

LM1

0002

0 C

itrat

e cy

cle

Met

abol

ism

; Car

bohy

drat

e 0.

0787

07

9 SD

HB

, ID

H3G

, SD

HD

, CS,

IDH

2, ID

H3B

, AC

LY, O

GD

H, M

DH

2

(TC

A c

ycle

) M

etab

olis

m

0461

0 C

ompl

emen

t and

O

rgan

ism

al S

yste

ms;

0.

0796

78

16

MB

L2, C

7, C

R1,

MA

SP2,

F13

A1,

F8,

C1R

, F13

B, V

WF,

FG

G, F

5, F

3,

coag

ulat

ion

casc

ades

Im

mun

e Sy

stem

C

D59

, TFP

I, C

FD, F

2R

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8 M

elan

oma

Hum

an D

isea

ses;

Can

cers

0.

0971

75

16

PIK

3CG

, FG

F7, M

AP2

K2,

MET

, RA

F1, C

DH

1, F

GF1

2, H

GF,

PTE

N, A

KT1

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CC

ND

1, M

APK

3, P

DG

FRA

, MD

M2,

PIK

3R3,

FG

F2

Add

ition

al T

able

3. C

ontin

ued.



Pathway Pathway names Classification P value Number of genes Included genesentry expressed in the pathways

00330 Arginine and proline Amino Acid 0.002131 7 ODC1, PYCR1, GOT1, P4HA2, GLUD2, metabolism Metabolism GLUD1, GAMT

00900 Terpenoid backbone Amino Acid 0.005931 4 FDPS, PMVK, ACAT2, ACAT1 biosynthesis Metabolism

00100 Steroid biosynthesis Cancers 0.00854 4 TM7SF2, DHCR24, FDFT1, SC4MOL

00071 Fatty acid metabolism Cell Growth and 0.018304 5 ACADVL, ACAA2, LOC648603, ACAT2, Death ACAT1, DCI

00072 Synthesis and Lipid Metabolism 0.020758 3 BDH2, ACAT2, ACAT1 degradation of ketone bodies

00250 Alanine, aspartate and Lipid Metabolism 0.043597 4 GOT1, GLUD2, GLUD1, ASNS glutamate metabolism

05200 Pathways in cancer Lipid Metabolism 0.074605 14 CKS1B, MET, SMAD3, ITGA3, FZD4, STAT3, FOS, CDKN1A, LAMA3, SLC2A1, KX3-1, FAS, WNT7A, MYC

04115 p53 signaling pathway Metabolism of Other 0.095163 5 CDKN1A, TP53I3, SERPINB5, FAS, Amino Acids ADD45A

00471 D-Glutamine and Metabolism of 0.098434 2 GLUD2, GLUD1 D-glutamate Terpenoids and metabolism Polyketides

Additional Table 4. Common significant pathways obtained from 3 prostate cancer cell datasets by meta-analysis.



Pathway Pathway names Classification Number of genes Included genesentry expressed in the pathways

00010 Glycolysis/ Metabolism; 6 ADH1A, ADH1B, ADH5, ALDH1B1, Gluconeogenesis Lipid Metabolism ALDH3B2, PGK1

00050 Starch and sucrose Metabolism; Amino 5 GAA, PYGL, PYGM, UGDH, UGP2 metabolism Acid Metabolism

00982 Drug metabolism Metabolism; Xenobiotics 11 ADH1A, ADH1B, ADH5, ALDH3B2, AOX1, Biodegradation and CYP3A4, CYP3A5, FMO5, GSTM3, GSTO1, Metabolism GSTP1

04010 MAPK signaling Environmental Information 17 CD14, CHUK, DUSP1, DUSP3, FLNA, FLNC, pathway Processing; Signal FOS, GRB2, JUND, MEF2C, MYC, NF1, NFKB2, Transduction NR4A1, PPP3CC, RRAS2, TGFB3

04510 Focal adhesion Environmental Information 28 BCL2, CAV2, CCND1, CCND2, COL6A1, COL6A2, Processing; Signal FLNA, FLNC, FLT1, GRB2, ILK, ITGA5, ITGA7, Transduction ITGB3, ITGB4, KDR, LAMA5, MET, MYLK, PAK4, PIK3R3, ROCK2, SHC1, SOS2, TLN1, TNC, TNXA, ZYX

04512 ECM-receptor Environmental Information 12 AGRN, CD44, COL6A1, COL6A2, ITGA5, ITGA7, interaction Processing; Signaling ITGB3, ITGB4, LAMA4, LAMA5, SDC2, TNC Molecules and Interaction

04530 Tight junction Environmental Information 9 CASK, CLDN3, CLDN4, CLDN5, INADL, MYH9, Processing; Signaling Molecules RKCD, RRAS2, SYMPK and Interaction

04540 Gap junction Cellular Processes; Cell Motility 8 CSNK1D, GJA1, GRB2, ITPR1, ITPR2, ITPR3, TUBA4A, TUBB2C

04810 Regulation of Cellular Processes; Cell Motility 15 BAIAP2, CD14, EZR, IQGAP1, IQGAP2, ITGA5, actin cytoskeleton ITGA7, ITGB3, ITGB4, MYH9, MYLK, PAK4, PIK3R3, ROCK2, RRAS2

04910 Insulin signaling Organismal Systems; 11 CALM1, FASN, GRB2, IRS1, PDE3B, PIK3R3, pathway Endocrine System PRKAA1, PYGL, PYGM, SHC1, TSC2

05200 Pathways in cancer Human Diseases; Cancers 19 ABL1, BCL2, CCND1, CDH1, CHUK, CTBP2, DAPK1, FOS, GRB2, GSTP1, JUP, KLK3, LAMA4, LAMA5, MYC, NFKB2, PIK3R3, TGFB3, TRAF4

05211 Renal cell Human Diseases; Cancers 5 GRB2, PAK4, PIK3R3, PTPN11, TGFB3 carcinoma

05214 Glioma Human Diseases; Cancers 5 CALM1, CCND1, GRB2, PIK3R3, SHC1

05220 Chronic myeloid Human Diseases; Cancers 11 ABL1, CCND1, CHUK, CTBP2, GRB2, MYC, leukemia PIK3R3, PTPN11, SHC1, SMAD3, TGFB3

05221 Acute myeloid Human Diseases; Cancers 6 CCND1, CHUK, GRB2, JUP, MYC, PIK3R3 leukemia

05222 Small cell lung Human Diseases; Cancers 9 BCL2, CCND1, CHUK, FHIT, LAMA4, LAMA5, cancer MYC, PIK3R3, TRAF4

Additional Table 5. Common crossing significant pathways between the results of GSEA and meta-analysis about prostate cancer tissues.



thw

ay

Path

way

nam

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ssifi

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In

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drat

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abol

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LC; P

pap2

b; U

GC

G; D

EGS1

;

M

etab

olis

m

Sptlc

2; A

SAH

1

Add

ition

al T

able

6A

. Enr

iche

d si

gnifi

cant

pat

hway

s ob

tain

ed fr

om th

e pu

blic

ally

ava

ilabl

e O

NC

OM

INE

canc

er g

ene

expr

essi

on m

icro

arra

y da

taba

se b

y G

SEA

up-

regu

late

d pa

thw

ays.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0065

0 B

utan

oate

met

abol

ism

M

etab

olis

m; C

arbo

hydr

ate

0.02

4 14

A

LDH

5A1;

ALD

H2;

ald

h3a2

; GA

D2;

had

h; E

chs1

; acs

m3;

AC

SM1;

ALD

H9A

1;

M

etab

olis

m

HM

GC

S2; H

AD

HA

; ALD

H7A

1; p

dhB

; pdh

A2

0071

0 C

arbo

n fix

atio

n in

M

etab

olis

m; E

nerg

y 0.

011

13

TPI1

; TPI

1P1;

FB

P2; P

GK

1; M

dh1;

Got

2; F

bp1;

ALD

OA

; tkt

; ME1

; Ald

ob;

ph

otos

ynth

etic

org

anis

ms

Met

abol

ism

LO

C65

2797

; PK

M2

0097

0 A

min

oacy

l-tR

NA

G

enet

ic In

form

atio

n 0.

002

11

Nar

s; K

AR

S; ra

rs; i

ars2

; Gar

s; fa

rsa;

AA

RS;

SA

RS;

epr

s; T

ars;

iars

bi

osyn

thes

is

Proc

essi

ng; T

rans

latio

n

0106

1 B

iosy

nthe

sis o

f -

0.00

1 37

LO

C10

0130

320;

sdhD

; pga

m1;

eno

2; H

K3;

sdhC

; pfk

p; M

dh1;

ALD

OA

; pdh

B;

ph

enyl

prop

anoi

ds

D

HA

; pdh

A2;

Ald

ob; S

dhB

; GPI

; HK

2P1;

Hk2

; AC

LY; A

CO

2; P

GK

1; C

S; F

bp1;

D

hfr;

Prdx

6; L

OC

1001

3304

2; G

APD

H; G

APD

HL6

; FH

; FB

P2; G

ot2;

eno

1;

IDH

1; ta

ldo1

; ID

H2;

tkt;

LOC

6527

97; P

KM

2

0106

5 B

iosy

nthe

sis o

f alk

aloi

ds

- 0.

023

41

LOC

1001

3032

0; sd

hD; p

gam

1; e

no2;

HK

3; sd

hC; P

GD

; BC

AT2;

pfk

p; M

dh1;

de

rived

from

his

tidin

e

H6p

d; p

rps2

; Prp

s1l1

; PR

PS1;

ALD

OA

; pdh

B; S

DH

A; p

dhA

2; A

ldob

; Sdh

B;

an

d pu

rine

ID

H3B

; GPI

; HK

2P1;

Hk2

; AC

LY; N

T5C

2; A

CO

2; P

GK

1; C

S; A

TIC

;

LOC

1001

3304

2; G

APD

H; G

APD

HL6

; Idh

3g; I

mpd

h2; e

no1;

IDH

1; ID

H2;

M

E1; L

OC

6527

97; P

KM

2

0107

0 B

iosy

nthe

sis o

f pla

nt

- 0.

008

50

SC5D

L; D

HC

R24

; LO

C10

0130

320;

sdhD

; pga

m1;

eno

2; M

VD

; HK

3; sd

hC;

ho

rmon

es

PG

D; F

DPS

; pfk

p; M

dh1;

H6p

d; p

rps2

; Prp

s1l1

; PRP

S1; A

LDO

A; p

dhB;

SD

HA

;

pdhA

2; A

ldob

; Sdh

B; t

m7s

f2; m

at1a

; ID

H3B

; GPI

; HK

2P1;

Hk2

; AC

LY; A

CO

2;

PGK

1; C

S; m

at2a

; ID

I1; A

TIC;

LO

C100

1330

42; G

APD

H; G

APD

HL6

; HM

GCS

2;

Idh3

g; G

ot2;

IDH

1; e

no1;

tald

o1; I

DH

2; tk

t; EB

P; L

OC6

5279

7; P

KM

2

0110

0 M

etab

olic

pat

hway

s -

0.00

1 42

2 AT

P6V

0E1;

HA

AO

; GU

K1;

Pla

2g2a

; ATP

6V1E

1; H

SD17

B2;

NFK

B1;

ald

h1a1

;

Pcyt

1a; C

YP3

A4;

PO

LR2G

; GA

LNS;

Apr

t; A

UH

; tyr

; TY

RL;

CH

ST1;

Atp

5j;

D

BH

; AH

CY

L1; H

K2P

1; H

k2; p

apss

1; P

OLR

2F; M

UT;

AC

O2;

AC

SL1;

IDI1

;

Fbp1

; gpa

a1; A

TP6V

1F; A

tp5c

1; L

OC

1001

3304

2; G

APD

H; G

APD

HL6

; Idh

3g;

ck

m; Q

PRT;

NO

S1; N

DU

FAB

1; a

ass;

rrm

2; a

tp5o

; ATP

5J2;

PN

LIPR

P1; t

k1;

O

DC

1; O

CR

L; A

KR

1D1;

PPT

1; P

afah

1b2;

Uqc

rc1;

CY

P2E1

; dao

; PTG

ES; i

ds;

Sa

t1; n

adK

; FA

SN; P

pap2

b; IT

PKA

; PO

LD4;

NO

S2; c

d38;

ptg

ds; H

PGD

S;

MTM

R1;

AG

PS; i

tpa;

ALD

H3A

1; p

gm1;

rdh1

1; S

T3G

AL1

; TPI

1; T

PI1P

1;

POLR

2L; C

YP4

F2; a

tp6v

1b2;

SD

HA

; ALD

H4A

1; S

dhB

; had

h; L

OC

4424

54;

LO

C72

7947

; UQ

CR

B; P

GK

1; L

dhA

; ATP

5G1;

hsd

17b4

; AK

R1B

1; C

OX

6B1;

AT

IC; a

oc3;

uqc

rfs1

; UQ

CR

FSL1

; PLA

2G10

; Ndu

fv2;

LO

C65

2797

; PK

M2;

N

DU

FS6;

MTM

R6;

XD

H; E

chs1

; LO

C10

0130

320;

sdhD

; SR

M; a

da; A

CSM

1;

cad;

Cyp

11b2

; Ald

h6a1

; Gal

ntl4

; ATP

6V1G

2; sg

pl1;

Ptg

s1; S

CP2

; Ndu

fs5;

LO

C10

0130

794;

Uqc

r11;

dct

D; P

IGC

; Im

pdh2

; tkt

; ALP

L; n

me3

; ALO

X12

B;

D

HC

R24

; ATP

6V0C

; NM

E2; N

ME1

-NM

E2; N

me1

; hpd

; B3G

NT2

; b3g

nt1;

PK1;

RPN

1; P

IGH

; PO

LR2H

; B3g

alt5

; ND

UFC

1; S

GSH

; Ogt

; ddc

; PLC

G2;

dh1c

; AD

H1B

; AD

H1A

; Ald

ob; N

DU

FA5;

ALD

H1A

3; P

LA2G

1B; N

OS3

;

PLA

2G5;

HA

DH

A; C

YP2

C19

; GLU

L; ID

H2;

B4G

ALT

1; U

QC

RQ

; agx

t;

Add

ition

al T

able

6A

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

GA

LC; A

NPE

P; M

AN

2A1;

RD

H16

; PI4

KB

; ALG

8; ld

hb; C

YP4

A11

; Spt

lc2;

ALD

H2;

Ndu

fb8;

CY

P2A

7; A

LOX

12; N

DU

FB1;

DPM

1; A

smt;

LTA

4H; e

no1;

PCC

B; A

caa1

; cox

17; A

CA

DSB

; UG

DH

; CO

X8A

; ATP

5B; L

OC

1001

3179

5;

en

o2; d

ct; n

nmt;

NT5

C2;

uck

l1; P

OLR

2B; C

YP1

9A1;

dut

; Rpn

2; a

tp5h

;

Atp

6v1a

; Cyp

1a2;

EB

P; A

TP6A

P1; M

AO

A; B

3gnt

3; U

GT2

B17

; DEG

S1; U

AP1

;

ATP6

V1D

; ATP

5G2;

Atp

5i; g

rhpr

; pai

cs; P

KLR

; Ptg

is; H

MG

CS2

; FH

; pcc

A;

ta

ldo1

; AK

R1A

1; G

AN

AB

; b3g

at2;

Ala

d; A

CY

1; P

PAP2

A; a

csm

3; C

YP2

C8;

AC

AD

M; N

ME4

; st8

sia5

; Nm

e6; g

ne; P

GD

; PLA

2G7;

Atp

6v0e

2; H

6pd;

ala

S2;

ID

O1;

Aan

at; P

RO

DH

2; O

AT; C

YP2

C18

; GA

A; F

AM

164A

; Ndu

fb7;

Dhf

r;

PCK

1; G

k2; P

ole;

epr

s; P

RO

DH

; FU

T3; a

hcY;

TPO

; SC

5DL;

ALP

I; PO

N3;

Aoc

2; A

MD

1; N

dufv

1; D

hrs3

; PIP

4K2B

; CO

X5B

; pdh

B; P

PAT;

mth

fd2;

Ndu

fb5;

FU

T5; m

at1a

; GU

SB; S

T3G

AL2

; AC

AD

VL;

GB

A; P

olr2

c; C

OA

SY;

ID

H1;

DG

KZ;

Khk

; Cox

7b; C

ox7c

; Atp

6v0b

; ALD

H9A

1; D

DO

ST; A

LAS1

;

GA

D2;

sorD

; Ndu

fs8;

LO

C15

1162

; Mga

t5; M

thfr

; Prd

x6; L

dhc;

FB

P2; A

ldh3

b1;

D

gkg;

GLU

D2;

ALD

H5A

1; B

4GA

LNT1

; spt

lc1;

hex

A; H

sd3b

2; H

K3;

pfk

p;

gc

k; N

ME2

; NM

E1-N

ME2

; Nm

e1; P

IP5K

1A; G

PI; I

NPP

4A; A

ASD

HPP

T;

ha

dhb;

AD

H5;

AD

H5P

4; A

TP6V

1G1;

CY

P3A

7; C

KB

; cyp

2a6;

CO

MT;

ATP6

V0A

2; b

hmT;

MA

N1A

2; C

YP2

1A2;

HA

O1;

UG

T2B

15; p

gam

1; R

EV3L

;

ND

UFA

1; M

VD

; CH

SY1;

CO

X6C

; CY

P2C

9; p

dxK

; Adh

1c; A

DH

1B; A

DH

1A;

G

NS;

Ndu

fa2;

ALD

OA

; hgd

; PO

LR2J

; CO

X5A

; CS;

Aca

cb; P

ikfy

ve; P

RIM

2;

K

ynu;

Acs

l6; P

cyt1

b; M

E1; D

AD

1; C

OX

4I1;

ndu

fs3;

Eph

x2; p

igl;

Ndu

fa7;

BC

AT2;

UG

T2B

7; IN

PP5A

; PLC

B2;

prp

s2; A

tp5a

1; C

ox6a

1; F

UT4

; cyc

1; M

PI;

SM

PD1;

ASA

H1;

CY

P27B

1; a

ldh3

a2; C

yp11

a1; C

DS1

; Uqc

rh; U

QC

RH

L;

Mdh

1; c

at; P

rps1

l1; P

RPS

1; A

tp5d

; ID

H3B

; mat

2a; P

afah

1b1;

MA

OB

; arg

2;

U

GP2

; Got

2; C

YP1

7A1;

Pip

5k1b

; cyp

2a13

; agl

; ALO

X15

B; C

YP1

1B1;

ND

UFS

4; C

ox6a

2; T

STA

3; C

ps1;

Pol

d2; b

4gal

t2; A

CSL

3; sd

hC; A

TP5G

3;

FD

PS; A

lppl

2; p

ts; C

YP3

A5;

Uqc

rc2;

UG

CG

; ptg

ds; H

PGD

S; p

dhA

2; tm

7sf2

;

AC

LY; S

C4M

OL;

CH

PF; M

GLL

; pol

d3; A

LOX

15; p

olr2

i; A

LDH

7A1;

ST6G

AL1

; AB

O; I

dua;

GA

LNT1

; GA

LNT1

3; p

igo

0301

0 R

ibos

ome

Gen

etic

Info

rmat

ion

0.00

0 21

8 rp

s20;

RPL

21P1

4; rp

l21;

RPL

21P2

0; R

PL21

P80;

RPL

21P1

19; R

PL21

P128

;

Pr

oces

sing

; Tra

nsla

tion

RPL

21P1

3; R

PL21

P105

; RPL

21P1

34; R

PL21

P93;

RPL

21P1

25; R

PL21

P16;

RPL

21P2

9; R

PL21

P28;

RPL

21P1

20; R

PL21

P87;

RPL

21P3

9; R

PL21

P98;

RPL

21P9

7; R

PL21

P69;

RPL

21P4

6; R

PL21

P37;

RPL

21P4

5; R

PL21

P53;

RPS

10P7

; RPS

10P1

1; rp

s10;

RPS

10P1

3; R

PS10

P4; R

PS10

P22;

RPL

18; r

pl24

;

RPL

24P6

; rpl

9; R

PL9P

25; R

PS24

; rps

13; R

PS13

P8; R

PS13

P2; R

PL10

AP9

;

RPL

10A

; RPL

10A

P6; R

PL37

; RPS

27A

P11;

RPS

27A

P12;

RPS

27A

;

RPS

27A

P16;

RPS

29P1

1; R

PS29

; RPS

29P9

; RPS

29P3

; RPS

29P1

7; R

PS29

P16;

rpl2

2; R

PL22

P11;

RPL

3; L

OC

6538

81; R

PL5P

34; r

pl5;

RPL

5P1;

Rpl

34; R

PL38

;

RPS

6P25

; RPS

6P1;

RPS

6; R

PS7P

10; R

PS7P

4; R

PS7P

11; r

ps7;

RPL

8P2;

rpl8

;

RPL

P0P6

; RPL

P0P2

; RPL

P0P3

; rpl

P0; S

NO

RA

7B; r

pl32

; Sno

ra7a

; RpL

30;

R

PL17

P18;

RPL

17P3

9; R

PL17

P7; R

PL17

P20;

LO

C72

9046

; RPL

17P3

3;

Add

ition

al T

able

6A

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

RPL

17P3

4; R

PL17

P9; R

PL17

P22;

RpL

17; R

PL17

P36;

RPS

9P4;

rps9

;

RPL

27A

; rps

12; R

PS12

P11;

RPS

12P4

; RPS

12P9

; rps

17; R

PL12

P6; R

PL12

P32;

RPL

12P1

4; rp

l12;

RPL

12P2

; RPL

12P3

5; R

PL12

P19;

RPS

15A

P12;

RPS

15A

P24;

R

PS15

AP1

1; R

PS15

AP1

7; R

PS15

AP1

9; R

PS15

A; r

ps19

; RPS

19P3

; RPS

28P6

;

RPS

28; R

PS28

P9; r

pl28

; RPS

4Y1;

RPL

31P1

7; rp

l31;

RPL

31P4

9; R

PL19

P12;

rpl1

9; F

au; r

ps23

; RPL

15P1

8; R

PL15

P17;

RPL

15P7

; RPL

15; R

PL15

P3;

R

PL15

P22;

RPL

35P2

; RPL

35P1

; rpl

35; R

PS8P

10; R

PS8P

8; rp

s8; r

ps21

;

RPL

41; R

PL37

A; R

pl27

; RPL

23A

P65;

RPL

23A

P44;

RPL

23A

P43;

RPL

23A

P63;

RPL

23A

P75;

RPL

23A

P37;

Rpl

23a;

RPS

15P5

; rps

15; r

pl11

; rpl

p1; R

ps5;

rpl2

3;

R

PL23

P6; R

PL7P

20; R

PL7;

RPL

7P32

; RPL

7P24

; RPL

7P23

; RPL

7P26

;

RPL

7P16

; RPS

2P17

; rps

2; R

PS2P

55; R

PS2P

8; R

PS2P

20; R

PS2P

11; R

PS2P

12;

R

PS2P

5; R

PS2P

51; R

PL13

; RPL

13P1

2; rp

l14;

RPS

25; R

PS25

P8; r

pl4;

RPL

4P4;

R

PL4P

5; R

PS16

P10;

RPS

16P1

; rps

16; r

ps11

; RPS

11P5

; RPL

29P1

1; R

PL29

P9;

R

PL29

P26;

rpl2

9; R

PL29

P12;

rps3

; RPS

3P3;

RPS

27P1

3; R

PS27

P19;

RPS

27P2

9; R

PS27

P6; r

ps27

; RPS

27P7

; RPS

27P2

1; R

PS27

P9; R

PS27

P23;

RPL

6P27

; rpl

6; R

PL6P

19; R

PL6P

10; L

OC

1001

3010

7; R

PS3A

P5; R

PS3A

P49;

LOC

1001

3169

9; R

PS3A

P47;

rps3

a; R

PS18

P12;

rps1

8; R

PS18

P5; R

PL36

AL;

R

PS4X

P13;

rps4

x; R

PS4X

P6

0305

0 Pr

otea

som

e G

enet

ic In

form

atio

n 0.

001

33

Psm

d11;

Psm

e4; P

SMB

5; p

smd3

; Psm

a3; p

smd7

; PSM

B10

; psm

b7; p

smc3

;

Pr

oces

sing

; Fol

ding

,

PS

MD

13; P

SMD

1; S

HFM

1; p

smc1

; LO

C64

3668

; PSM

D8;

PSM

B3;

PSM

A1;

Sorti

ng a

nd D

egra

datio

n

Ps

ma4

; psm

A2;

PSM

C2;

psm

c4; L

OC

6528

26; P

SMD

2; P

SMD

14; P

SMD

4;

PSM

E2; P

SME1

; psm

b8; p

smb2

; PSM

C5;

PSM

B4;

Psm

c6; p

smb1

0341

0 B

ase

exci

sion

repa

ir G

enet

ic In

form

atio

n 0.

001

13

pcnA

; MB

D4;

lig3

; par

p1; P

OLD

4; p

old3

; OG

G1;

mpg

; HM

GB

1; H

MG

B1L

10;

Proc

essi

ng; R

eplic

atio

n

Po

le; P

old2

; Ape

x1

an

d R

epai

r

0412

0 U

biqu

itin

med

iate

d G

enet

ic In

form

atio

n 0.

000

46

UB

E2N

; UB

R5;

LO

C73

0429

; FZR

1; H

UW

E1; B

IRC

3; L

OC

1001

3297

3;

prot

eoly

sis

Proc

essi

ng; F

oldi

ng,

TCEB

1; U

BE2

I; m

dm2;

AN

APC

5; T

rip12

; btrc

; ube

2d2;

WW

P1; T

ceb2

; par

k2;

Sorti

ng a

nd D

egra

datio

n

D

DB

1; c

dc20

; UB

E2E1

; Ube

3a; W

WP2

; Skp

2; p

pil2

; birc

2; U

BE2

D1;

Uba

1;

UB

E2J1

; vhl

; Ned

d4l;

Cbl

b; u

be2l

3; u

be4a

; UB

E2G

2; m

grn1

; AN

APC

13;

C

DC

16; U

BE3

B; S

ocs1

; PIA

S1; U

BA

2; u

ba3;

SK

P1; F

bxw

11; U

be2s

; SIA

H1

0414

2 Ly

soso

me

Cel

lula

r Pro

cess

es;

0.00

9 55

A

tp6v

0b; A

TP6V

0C; C

D16

4; C

TSL1

; lam

p1; C

TSB

; SG

SH; G

ALN

S;

Tr

ansp

ort a

nd C

atab

olis

m

SLC

11A

1; G

NS;

Cltb

; AC

P2; T

PP1;

Gga

2; li

pA; C

TSZ;

GA

A; c

tsf;

ap3s

1;

CTS

H; A

TP6A

P1; C

TSD

; fuc

A1;

LG

MN

; CD

63; C

TSG

; CLT

A; G

ALC

;

LAPT

M5;

PLA

2G15

; PPT

1; h

exA

; Neu

1; A

P3B

2; A

BC

A2;

PSA

P; A

p3d1

;

GU

SB; A

bcb9

; Lap

tm4b

; GB

A; L

AM

P3; A

P1S1

; SM

PD1;

ids;

Cts

k; A

SAH

1;

Sort1

; CTS

E; A

P1B

1; Id

ua; A

TP6V

0A2;

LA

PTM

4A; l

amp2

; gm

2a

0501

0 A

lzhe

imer

’s d

isea

se

Hum

an D

isea

ses;

0.

001

104

Cac

na1f

; NO

S2; C

OX

8A; B

ID; A

TP5B

; CY

CS;

IL1B

; CA

PN1;

ND

UFA

1;

N

euro

dege

nera

tive

Cal

ml3

; TN

F; B

ad; N

DU

FC1;

APO

E; L

OC

1001

2950

0; A

paf1

; CO

X6C

; Uqc

rh;

Dis

ease

s

U

QC

RH

L; N

dufa

2; C

APN

2; A

tp5d

; Atp

5j; S

DH

A; G

RIN

2A; S

dhB

; ND

UFA

5;

Add

ition

al T

able

6A

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

CA

LM3;

CA

LM2;

CA

LM1;

LO

C44

2454

; LO

C72

7947

; UQ

CR

B; C

OX

5A;

AT

P5G

1; C

ALM

3; C

ALM

2; C

ALM

1; N

dufs

8; R

YR

3; p

pp3c

a; C

OX

6B1;

Atp

5c1;

Ndu

fb7;

NO

S3; a

tp5h

; LO

C10

0133

042;

GA

PDH

; GA

PDH

L6;

uq

crfs

1; U

QCR

FSL1

; grin

2c; A

PP; C

acna

1d; N

dufv

2; C

ASP

8; N

OS1

; ND

UFA

B1;

A

DA

M10

; ND

UFS

6; a

tp5o

; map

t; LO

C100

1303

20; s

dhD

; UQ

CRQ

; ND

UFS

4;

Co

x6a2

; ndu

fs3;

CO

X4I

1; A

TP2A

2; C

OX

7A1;

Cdk

5r1;

ATP

5G2;

Ndu

fv1;

Ndu

fa7;

sdhC

; Fas

; chp

2; A

TP5G

3; P

LCB2

; Uqc

rc1;

Cox

7a2l

; Uqc

rc2;

CA

CNA

1S; C

OX

5B; C

ox6a

1; A

tp5a

1; N

dufb

5; N

dufb

8; c

yc1;

Ndu

fs5;

LO

C100

1307

94; C

OX

7A2;

Uqc

r11;

ND

UFB

1; L

OC1

0013

1098

; CA

CNA

1C;

IT

PR1;

PPP

3CC;

Nae

1; P

sen1

; Cox

7b; G

NA

Q; C

ox7c

0501

2 Pa

rkin

son’

s dis

ease

H

uman

Dis

ease

s;

0.00

1 82

C

OX

8A; A

TP5B

; CY

CS;

ND

UFA

1; N

DU

FC1;

Apa

f1; p

ark2

; CO

X6C

; Uqc

rh;

Neu

rode

gene

rativ

e

U

QC

RH

L; N

dufa

2; A

tp5d

; Atp

5j; S

DH

A; S

dhB

; ND

UFA

5; P

AR

K7;

LO

C44

2454

;

D

isea

ses

LOC

7279

47; U

QC

RB

; CO

X5A

; ATP

5G1;

Uba

1; S

LC25

A6;

UB

E2J1

; HTR

A2;

N

dufs

8; C

OX

6B1;

Atp

5c1;

Ndu

fb7;

UB

E2G

2; a

tp5h

; uqc

rfs1;

UQ

CR

FSL1

;

slc6a

3; N

dufv

2; N

DU

FAB

1; N

DU

FS6;

atp

5o; L

OC

1001

3032

0; sd

hD; U

QC

RQ

;

Cox

6a2;

ND

UFS

4; n

dufs

3; C

OX

4I1;

SLC

25A

5; S

LC25

A5P

8; C

OX

7A1;

RPS

27A

P11;

RPS

27A

P12;

RPS

27A

; RPS

27A

P16;

Ndu

fv1;

ATP

5G2;

vda

c2;

N

dufa

7; sd

hC; A

TP5G

3; U

qcrc

1; C

ox7a

2l; U

qcrc

2; C

OX

5B; C

ox6a

1; A

tp5a

1;

N

dufb

5; N

dufb

8; c

yc1;

Ndu

fs5;

LO

C10

0130

794;

VD

AC

1P1;

VD

AC

1; C

OX

7A2;

Uqc

r11;

SLC

18A

1; u

be2l

3; N

DU

FB1;

SLC

18A

2; V

DA

C3; C

ox7b

; Cox

7c; S

LC25

A4

0501

6 H

untin

gton

’s d

iseas

e H

uman

Dise

ases

; 0.

001

100

CO

X8A

; ATP

5B; C

YC

S; C

REB

3L2;

ND

UFA

1; N

RF1

; CR

EB1;

Hap

1; P

OLR

2G;

Neu

rode

gene

rativ

e

N

DU

FC1;

PO

LR2H

; Apa

f1; C

OX

6C; G

rm5;

PO

LR2L

; Uqc

rh; U

QCR

HL;

Ndu

fa2;

D

isea

ses

Atp

5d; A

tp5j

; HD

AC

2; S

DH

A; C

ltb; S

dhB

; DN

AH

3; P

OLR

2J; N

DU

FA5;

POLR

2F; t

p53;

LO

C44

2454

; LO

C72

7947

; UQ

CR

B; P

OLR

2B; C

OX

5A;

AT

P5G

1; S

LC25

A6;

Ndu

fs8;

CO

X6B

1; A

tp5c

1; N

dufb

7; a

tp5h

; uqc

rfs1;

UQ

CR

FSL1

; DLG

4; B

AX

; Ndu

fv2;

CA

SP8;

ND

UFA

B1;

SO

D1;

GPX

1;

N

DU

FS6;

atp

5o; C

LTA

; LO

C10

0130

320;

sdhD

; UQ

CR

Q; N

DU

FS4;

Cox

6a2;

nd

ufs3

; CO

X4I

1; S

LC25

A5;

SLC

25A

5P8;

CO

X7A

1; A

P2S1

; ATP

5G2;

Ndu

fv1;

vdac

2; N

dufa

7; sd

hC; A

TP5G

3; A

P2M

1; P

LCB

2; U

qcrc

1; C

ox7a

2l; U

qcrc

2;

CO

X5B

; Cox

6a1;

Atp

5a1;

Ndu

fb5;

tgm

2; N

dufb

8; c

yc1;

Ndu

fs5;

LO

C100

1307

94;

V

DA

C1P1

; VD

AC1

; CO

X7A

2; U

qcr1

1; P

olr2

c; D

CTN

2; sp

1; N

DU

FB1;

Hda

c1;

po

lr2i;

ITPR

1; V

DA

C3; C

ox7b

; GN

AQ

; Cox

7c; S

LC25

A4

0511

0 V

ibrio

cho

lera

e H

uman

Dis

ease

s;

0.00

1 30

AT

P6V

0E1;

Atp

6v0b

; Gna

s; m

uc2;

ATP

6V0C

; ATP

6V1E

1; A

CTG

1; A

TP6V

1D;

in

fect

ion

Infe

ctio

us D

isea

ses

CFT

R; A

rf1;

ATP

6V1G

2; S

EC61

B; P

rkca

; PLC

G2;

atp

6v1b

2; P

RK

AC

A;

A

tp6v

0e2;

PR

KC

B; K

DEL

R1;

ATP

6V1F

; KD

ELR

2; P

RK

CG

; ATP

6V1G

1;

A

tp6v

1a; P

dia4

; KC

NQ

1; A

CTB

; ATP

6V0A

2; se

c61g

; ATP

6AP1

0513

0 Pa

thog

enic

H

uman

Dis

ease

s;

0.01

0 35

C

DH

1; Y

WH

AZ;

ncl

; KRT

18P1

9; K

RT18

; KRT

18P2

6; c

ttn; A

CTG

1; T

UB

B2C

;

Esch

eric

hia

coli

Infe

ctio

us D

isea

ses

Rho

a; P

rkca

; yw

haq;

Tub

b4; t

ubb2

b; N

CK

2; A

BL1

; TU

BA

4A; C

TNN

B1;

WA

S;

in

fect

ion

LO

C39

9942

; TU

BA

1B; T

ubb2

a; E

ZR; L

OC

1001

2965

2; C

dc42

; CD

C42

P2;

O

cln;

LO

C64

7859

; WA

SL; A

CTB

; MC

1R; t

ubb3

; TU

BA

3E; A

RPC

5; It

gb1

Add

ition

al T

able

6A

. Con

tinue

d.



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0005

2 G

alac

tose

met

abol

ism

M

etab

olis

m; C

arbo

hydr

ate

0.00

0 13

B

4GA

LT1;

Lct

; pgm

1; H

K2P

1; H

k2; H

K3;

UG

P2; p

fkp;

GA

A; L

ALB

A;

Met

abol

ism

A

KR

1B1;

gck

; b4g

alt2

0035

0 Ty

rosi

ne m

etab

olis

m

Met

abol

ism

; Am

ino

Aci

d 0.

011

29

TPO

; Wbs

cr22

; ALD

H1A

3; M

AO

A; A

oc2;

LO

C28

4889

; hpd

; dct

; MA

OB

;

M

etab

olis

m

AD

H5;

AD

H5P

4; e

ch1;

ALD

H3A

1; a

oc3;

ddc

; Ald

h3b1

; CO

MT;

Got

2; ty

r;

TYR

L; A

dh1c

; AD

H1B

; AD

H1A

; Adh

1c; A

DH

1B; A

DH

1A; L

CM

T2; D

BH

; hgd

0056

2 In

osito

l pho

spha

te

Met

abol

ism; C

arbo

hydr

ate

0.00

8 18

IT

PKA

; IN

PP4A

; PIK

3CD

; OCR

L; P

IK3C

G; P

ikfy

ve; I

TPK

1; A

ldh6

a1; P

IP4K

2B;

m

etab

olis

m

Met

abol

ism

Pi

k3cb

; TPI

1; T

PI1P

1; P

I4K

B; I

NPP

5A; P

LCG

2; P

LCB

2; P

ip5k

1b; P

IP5K

1A

0059

0 A

rach

idon

ic a

cid

Met

abol

ism

; Lip

id

0.00

0 29

A

LOX

12B

; ALO

X15

B; P

la2g

2a; C

YP2

C8;

Eph

x2; p

tgds

; HPG

DS;

CY

P4F2

;

met

abol

ism

M

etab

olis

m

CY

P2C

9; G

PX4;

ptg

ds; H

PGD

S; C

YP4

A11

; PTG

S2; g

pX3;

GPX

2; C

YP2

E1;

PT

GES

; Ptg

s1; C

YP2

C18

; PLA

2G1B

; ALO

X12

; ALO

X15

; Ptg

is; P

LA2G

5;

PL

A2G

10; C

YP2

C19

; LTA

4H; G

PX1

0059

1 Li

nole

ic a

cid

Met

abol

ism

; Lip

id

0.00

5 14

C

YP2

E1; P

la2g

2a; C

YP2

C18

; CY

P2C

8; P

LA2G

1B; A

LOX

15; C

YP3

A4;

met

abol

ism

M

etab

olis

m

PLA

2G5;

PLA

2G10

; CY

P3A

7; C

YP2

C19

; CY

P2C

9; C

YP3

A5;

Cyp

1a2

0083

0 R

etin

ol m

etab

olis

m

Met

abol

ism

; Met

abol

ism

of

0.00

1 29

C

YP2

A7;

UG

T2B

15; C

YP2

C18

; CY

P2C

8; C

YP1

A1;

UG

T2B

17; a

ldh1

a1;

Cof

acto

rs a

nd V

itam

ins

Dhr

s3; A

DH

5; A

DH

5P4;

CY

P3A

4; rd

h11;

RD

H16

; CY

P3A

7; C

yp26

a1; c

yp2a

6;

UG

T2B

7; C

YP2

C19

; CY

P2C

9; C

YP3

A5;

Cyp

1a2;

Adh

1c; A

DH

1B; A

DH

1A;

A

dh1c

; AD

H1B

; AD

H1A

; cyp

2a13

; CY

P4A

11

0098

0 M

etab

olis

m o

f M

etab

olis

m; X

enob

iotic

s 0.

000

36

CY

P2C

8; U

GT2

B15

; GST

M5;

UG

T2B

17; A

LDH

3A1;

CY

P3A

4; U

GT2

B7;

xeno

biot

ics b

y B

iode

grad

atio

n an

d

C

YP2

C9;

GST

O1;

CY

P3A

5; A

dh1c

; AD

H1B

; AD

H1A

; Adh

1c; A

DH

1B;

cy

toch

rom

e P4

50

Met

abol

ism

A

DH

1A; G

STA

4; C

YP2

E1; A

LDH

1A3;

CY

P2C

18; g

sta1

; gst

A2;

CY

P1A

1;

G

STM

3; C

YP2

F1; M

gst3

; AD

H5;

AD

H5P

4; G

STP1

; CY

P3A

7; A

ldh3

b1;

C

YP2

C19

; GST

T1; C

yp1a

2; m

gst2

; CY

P1B

1

0098

2 D

rug

met

abol

ism

-

Met

abol

ism

; Xen

obio

tics

0.00

0 40

M

AO

A; C

YP2

C8;

UG

T2B

15; G

STM

5; U

GT2

B17

; ALD

H3A

1; C

YP3

A4;

cyto

chro

me

P450

B

iode

grad

atio

n an

d

U

GT2

B7;

CY

P2C

9; G

STO

1; C

YP3

A5;

Adh

1c; A

DH

1B; A

DH

1A; A

dh1c

;

M

etab

olis

m

AD

H1B

; AD

H1A

; GST

A4;

CY

P2E1

; CY

P2A

7; A

LDH

1A3;

CY

P2C

18; g

sta1

;

gstA

2; c

yp2d

6; F

MO

1; G

STM

3; M

gst3

; MA

OB

; AD

H5;

AD

H5P

4; G

STP1

;

CY

P3A

7; c

yp2a

6; A

ldh3

b1; C

YP2

C19

; Cyp

1a2;

GST

T1; m

gst2

; cyp

2a13

0098

3 D

rug

met

abol

ism

-

Met

abol

ism

; Xen

obio

tics

0.00

5 17

G

USB

; XD

H; u

ckl1

; tk1

; CY

P2A

7; U

GT2

B15

; UG

T2B

17; C

ES1;

itpa

;

othe

r enz

ymes

B

iode

grad

atio

n an

d

C

YP3

A4;

CY

P3A

7; c

yp2a

6; U

GT2

B7;

Impd

h2; C

YP3

A5;

tpm

T; c

yp2a

13

M

etab

olis

m

0332

0 PP

AR

sign

alin

g pa

thw

ay

Org

anis

mal

Sys

tem

s;

0.01

6 32

R

PS27

AP1

1; R

PS27

AP1

2; R

PS27

A; R

PS27

AP1

6; fa

bp3;

; A

CA

DM

; slc

27a2

;

En

docr

ine

Syst

em

aqp7

; Cpt

1b; C

HK

B; P

PAR

A; A

CSL

3; IL

K; P

ltp; F

AD

S2; R

XR

G; C

YP4

A11

;

DB

I; A

POC

3; P

LIN

1; S

CP2

; AC

SL1;

Fab

p6; F

abp7

; AD

IPO

Q; H

MG

CS2

;

RX

RA

; PC

K1;

Gk2

; Acs

l6; A

caa1

; ME1

0401

0 M

APK

sign

alin

g pa

thw

ay

Envi

ronm

enta

l Inf

orm

atio

n 0.

001

138

Cac

na1f

; map

2k6;

Rap

1b; A

CV

R1B

; dus

p6; F

LNB

; Pdg

fb; P

la2g

2a; D

usp7

;

Pr

oces

sing

; Sig

nal

PPM

1A; N

FATC

4; IL

1B; N

FKB

1; M

AP4

K1;

DU

SP1;

map

k8; R

ASG

RF1

;

Tr

ansd

uctio

n

PT

PN7;

FG

F5; L

OC

4078

35; M

ap2k

2; F

LNC

; tp5

3; T

gfbr

2; F

GF1

8; M

AP3

K5;

Add

ition

al T

able

6B

. D

own-

regu

late

d pa

thw

ays.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

PL

A2G

1B; M

ap2k

5; M

YC

; ppp

3ca;

TG

FB3;

PR

KC

G; P

LA2G

5; F

GF2

;

Fgf3

; RA

F1; m

apt;

MA

PK10

; DU

SP9;

SO

S1; p

tprr

; NFK

B2;

CR

KL;

Srf

;

Stk3

; Pdg

frb;

Fas

; chp

2; C

AC

NB

4; F

OS;

Prk

ca; e

lk1;

MA

P3K

7; C

AC

NB

2;

R

RA

S2; L

OC

1001

3321

1; G

add4

5b; K

IAA

1549

; tab

2; M

AP3

K13

; Ras

grp2

;

FGF4

; LO

C10

0131

098;

CA

CN

A1C

; PPP

3CC

; RA

PGEF

2; L

OC

1001

3356

7;

C

AC

NG

1; N

R4A

1; D

USP

3; F

GF8

; FG

F9; r

ac1;

STM

N1;

relA

; Gad

d45g

;

FASL

G; G

AD

D45

A; d

usp5

; TN

F; P

ak2;

TA

OK

3; N

F1; a

kt1;

FLN

A; P

RK

AC

A;

ra

sgrp

3; M

APK

APK

2; R

PS6K

A2;

LO

C10

0127

984;

Kra

s; C

AC

NA

1E; J

un;

M

AP3

K4;

PLA

2G10

; Cac

na1d

; CA

CN

G3;

Il1r

1; H

SPA

8; M

apk8

ip2;

CA

CN

A1G

; FG

FR2;

MEF

2C; A

TF4;

ATF

4C; p

dgfr

a; m

apka

pk3;

JUN

D;

tg

fbr1

; Hsp

a1l;

NTR

K1;

Map

k14;

Map

k11;

CA

CN

B1;

Fgf

r1; C

AC

NA

1S;

PR

KC

B; M

AX

; ELK

4; a

kt2;

TG

FB1;

Rra

s; H

SPA

1A; H

SPA

1B; f

gf12

; Cdc

42;

C

DC

42P2

; MK

NK

2; ik

bkg;

Gna

12; C

acna

2d1;

Hsp

b1; H

SPB

L2; N

TRK

2;

SO

S2; F

gf7;

LO

C10

0132

771;

FG

F7P2

0401

2 Er

bB si

gnal

ing

path

way

En

viro

nmen

tal I

nfor

mat

ion

0.01

5 47

C

AM

K2G

; MA

PK10

; gab

1; T

GFA

; Pak

3; P

IK3C

D; S

OS1

; PIK

3CG

; CR

KL;

Pr

oces

sing

; Sig

nal

PIK

3R3;

Pak

2; B

ad; P

rkca

; akt

1; S

HC

1; P

LCG

2; e

lk1;

map

k8; E

rbb3

; PR

KC

B;

Tran

sduc

tion

LOC

4078

35; M

ap2k

2; N

rg2;

NC

K2;

AB

L1; R

PS6K

B1;

akt

2; K

IAA

1549

;

Cam

k2a;

Cam

k2b;

Erb

b4; K

ras;

CD

KN

1A; C

blb;

Sta

t5b;

MY

C; C

DK

N1B

; Jun

;

PRK

CG

; SH

C2;

Pik

3cb;

SH

C3;

PIK

3R2;

SO

S2; R

AF1

; NR

G1;

Erb

b2

0402

0 C

alci

um si

gnal

ing

Envi

ronm

enta

l Inf

orm

atio

n 0.

013

98

CA

MK

2G; C

acna

1f; S

LC8A

2; T

acr1

; ITP

KA

; BD

KR

B2;

P2R

X1;

NO

S2;

pa

thw

ay

H

TR4;

cd3

8; A

DC

Y2;

Agt

r1; H

TR6;

P2R

X6;

Cal

ml3

; HTR

7; L

HC

GR

;

AD

RA

1A; H

TR2A

; PLC

G2;

Grm

5; M

YLK

; PR

KA

CA

; cam

k4; G

RIN

2A;

C

ALM

3; C

ALM

2; C

ALM

1; E

DN

RA

; atp

2b4;

CA

LM3;

CA

LM2;

CA

LM1;

SLC

25A

6; T

rpc1

; Erb

b4; C

CK

AR

; RY

R3;

ppp

3ca;

NO

S3; C

AC

NA

1E; P

2rx5

;

PRK

CG

; ATP

2B2;

grin

2c; g

nal;

Cac

na1d

; GR

M1;

CC

KB

R; A

VPR

1B; N

OS1

;

SLC

8A1;

grp

r; C

AC

NA

1G; G

nas;

AD

CY

1; A

tp2b

3; D

RD

5; S

LC25

A5;

SLC

25A

5P8;

pdg

fra;

ATP

2A2;

tbxa

2r; P

TGER

3; N

tsr1

; P2R

X4;

vda

c2; P

dgfr

b;

ch

p2; P

TAFR

; Prk

ca; E

rbb3

; PLC

B2;

CA

CN

A1S

; PR

KC

B; T

AC

R3;

Adr

b3;

V

DA

C1P

1; V

DA

C1;

Cam

k2a;

ATP

2B1;

Cam

k2b;

AD

RA

1D; p

de1b

;

LOC

1001

3109

8; C

AC

NA

1C; P

PP3C

C; I

TPR

1; P

hkb;

VD

AC

3; C

HR

M3;

adra

1b; A

DR

B2;

GN

A11

; GN

AQ

; Pde

1c; E

rbb2

; SLC

25A

4

0406

0 C

ytok

ine-

cyto

kine

En

viro

nmen

tal I

nfor

mat

ion

0.02

2 11

9 cs

f1; I

FNA

6; A

CV

R1B

; eda

; Pdg

fb; I

L10R

A; I

L1B

; CC

L14;

CC

L15;

Tnf

sf11

;

rece

ptor

inte

ract

ion

Proc

essi

ng; S

igna

ling

IL18

RA

P; L

EP; C

SF3;

CX

CR

6; C

CR

2; T

gfbr

2; C

XC

R3;

TN

FSF9

; CSF

2RB

;

M

olec

ules

and

Inte

ract

ion

CC

L4L1

; CC

L4L2

; CX

CL1

; TG

FB3;

LEP

R; T

NFR

SF25

; csf

3r; C

CR

7; C

CL3

;

Il5; T

PO; c

cl1;

Cxc

l3; i

l10;

CC

L22;

ZFP

91; C

NTF

; Zfp

91-C

ntf;

Ccl

2; P

RLR

;

Tnfr

sf4;

INH

BC

; Pdg

frb;

Fas

; CD

40LG

; il2

rg; I

L8; H

gf; l

ta; I

l5ra

; FLT

1; Il

24;

If

na14

; CC

R1;

IFN

W1;

TN

FSF4

; IFN

A4;

IL13

; CX

CL5

; Il3

; Veg

fb; C

XC

L2;

X

CL2

; LTB

R; C

XC

R2;

CD

27; F

LT3;

Inhb

b; L

OC

6527

99; L

OC

6538

82;

K

IT; I

L9R

; EPO

R; I

FNG

R2;

FA

SLG

; IL4

; OSM

R; T

NF;

IL6S

T; C

XC

L12;

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

Il1

8r1;

IFN

A21

; CC

R9;

INH

BA

; Ifn

a10;

Ccl

27; T

NFR

SF21

; GD

F5; I

FNA

5;

IL

17A

; Cd7

0; C

XC

R5;

Il1r

1; g

h2; i

l1ra

p; IF

NG

R1;

ccr

4; T

NFS

F10;

TN

FRSF

8;

IL

7R; C

CL5

; pdg

fra;

IL6;

CC

L23;

Cxc

r1; c

tf1; t

gfbr

1; T

nfrs

f11a

; MET

;

CX

CR

4; Il

10rb

; EPO

; TG

FB1;

IL23

A; C

CL1

6; V

EGFA

; CC

L13;

ifna

2;

TN

FRSF

10C

; TN

FRSF

17

0406

2 C

hem

okin

e si

gnal

ing

Org

anis

mal

Sys

tem

s;

0.02

0 83

JA

K3;

rac1

; Rap

1b; r

elA

; fox

o3b;

FO

XO

3; P

RK

CD

; Par

d3; A

DC

Y2;

PIK

3CG

;

path

way

Im

mun

e Sy

stem

N

FKB

1; C

CL1

4; C

CL1

5; R

hoa;

akt

1; S

HC

1; C

XC

L12;

AD

RB

K1;

PR

KA

CA

;

CX

CR

6; C

CR

2; C

CR

9; C

cl27

; CX

CR

3; W

AS;

Kra

s; C

CL4

L1; C

CL4

L2;

C

XC

L1; g

ng5;

SH

C2;

tiam

1; C

XC

R5;

Pik

3cb;

SH

C3;

PX

N; g

nb2;

GN

B1;

CC

R7;

RA

F1; L

OC

1001

2815

5; C

CL3

; DO

CK

2; N

FKB

IA; c

cr4;

ccl

1; C

xcl3

;

AD

CY

1; C

CL5

; SO

S1; P

IK3C

D; C

xcr1

; CC

L23;

CC

L22;

CR

KL;

Ccl

2; S

TAT1

;

PIK

3R3;

IL8;

gng

7; P

LCB

2; P

RK

CB

; CX

CR

4; a

kt2;

STA

T2; K

IAA

1549

;

CC

R1;

Sta

t5b;

CX

CL5

; CC

L16;

Sta

t3; C

CL1

3; C

dc42

; CD

C42

P2; R

asgr

p2;

C

XC

L2; i

kbkg

; XC

L2; W

ASL

; PIK

3R2;

CX

CR

2; g

nb3;

SO

S2

0407

0 Ph

osph

atid

ylin

osito

l En

viro

nmen

tal I

nfor

mat

ion

0.00

0 31

IT

PKA

; PIK

3CD

; PIK

3CG

; OC

RL;

CD

S1; C

alm

l3; P

IK3R

3; IT

PK1;

PIP

4K2B

;

sign

alin

g sy

stem

Pr

oces

sing

; Sig

nal

Prkc

a; P

I4K

B; P

LCG

2; IN

PP5A

; PLC

B2;

PR

KC

B; P

IP5K

1A; C

ALM

3;

Tran

sduc

tion

CA

LM2;

CA

LM1;

CA

LM3;

CA

LM2;

CA

LM1;

INPP

4A; P

ikfy

ve; P

RK

CG

;

Pik3

cb; I

TPR

1; P

IK3R

2; D

GK

Z; P

ip5k

1b; D

gkg

0411

5 p5

3 si

gnal

ing

path

way

C

ellu

lar P

roce

sses

; Cel

l 0.

006

34

Gad

d45g

; EI2

4; G

AD

D45

A; B

ID; C

CN

D1;

CY

CS;

mdm

2; M

DM

4; F

as;

Gro

wth

and

Dea

th

Apa

f1; T

hbs1

; LO

C65

1610

; ATM

; SER

PIN

B5;

LO

C64

8152

; LO

C65

1921

; ATR

;

CC

NB

2; C

dk6;

Gad

d45b

; GTS

E1; t

p53;

CC

ND

2; ig

fbp3

; CD

KN

1A; T

SC2;

CC

NG

2; B

AX

; SER

PIN

E1; I

gf1;

CA

SP8;

SFN

; rrm

2; S

IAH

1

0414

0 R

egul

atio

n of

aut

opha

gy

Cel

lula

r Pro

cess

es;

0.01

4 13

If

na14

; BEC

N1;

Ifna

10; I

FNA

6; G

AB

AR

AP;

ifna

2; G

AB

AR

APL

2; IF

NA

4;

Tr

ansp

ort a

nd C

atab

olis

m

IFN

A21

; GA

BA

RA

PL3;

GA

BA

RA

PL1;

IFN

A5;

Ulk

2

0415

0 m

TOR

sign

alin

g pa

thw

ay

Envi

ronm

enta

l Inf

orm

atio

n 0.

002

24

RPS

6KB

1; H

IF1A

; RPS

6P25

; RPS

6P1;

RPS

6; a

kt2;

KIA

A15

49; d

dit4

; EIF

4B;

Proc

essi

ng; S

igna

l

EI

F4B

P7; P

IK3C

D; R

PS6K

A2;

LO

C10

0127

984;

PIK

3CG

; TSC

2; V

EGFA

;

Tr

ansd

uctio

n

Ve

gfb;

PIK

3R3;

rheb

; Pik

3cb;

akt

1; Ig

f1; P

IK3R

2; U

lk2

0427

0 Va

scul

ar sm

ooth

mus

cle

Org

anis

mal

Sys

tem

s;

0.00

0 63

C

acna

1f; P

RK

CD

; Pla

2g2a

; prk

cq; A

DC

Y2;

Agt

r1; C

alm

l3; A

RH

GEF

12;

co

ntra

ctio

n C

ircul

ator

y Sy

stem

A

DR

A1A

; Rho

a; M

YLK

; PR

KA

CA

; LO

C40

7835

; Map

2k2;

Gna

13;

C

ALM

3; C

ALM

2; C

ALM

1; E

DN

RA

; CA

LM3;

CA

LM2;

CA

LM1;

PLA

2G1B

;

PTG

IR; P

RK

CG

; PLA

2G5;

PLA

2G10

; PPP

1R12

B; R

AM

P1; C

acna

1d;

AV

PR1B

; RA

F1; M

YH

11; A

DC

Y1;

Gna

s; P

pp1c

c; P

PP1R

12A

; MY

L6B

;

Ppp1

ca; P

rkca

; Prk

ce; a

cta2

; PLC

B2;

CA

CN

A1S

; NPR

1; C

YP4

A11

; PR

KC

B;

K

IAA

1549

; AD

RA

1D; A

RH

GEF

11; A

ctg2

; CA

LD1;

LO

C10

0131

098;

CA

CN

A1C

; Gna

12; I

TPR

1; G

UC

Y1A

3; a

dra1

b; G

NA

11; G

UC

Y1A

2; G

NA

Q;

K

CN

MA

1; M

YL9

0431

0 W

nt si

gnal

ing

path

way

En

viro

nmen

tal I

nfor

mat

ion

0.00

0 59

C

AM

K2G

; rac

1; c

snk1

a1; C

CN

D1;

NFA

TC4;

btrc

; SFR

P4; R

hoa;

Ctb

p1;

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

Il1

8r1;

IFN

A21

; CC

R9;

INH

BA

; Ifn

a10;

Ccl

27; T

NFR

SF21

; GD

F5; I

FNA

5;

IL

17A

; Cd7

0; C

XC

R5;

Il1r

1; g

h2; i

l1ra

p; IF

NG

R1;

ccr

4; T

NFS

F10;

TN

FRSF

8;

IL

7R; C

CL5

; pdg

fra;

IL6;

CC

L23;

Cxc

r1; c

tf1; t

gfbr

1; T

nfrs

f11a

; MET

;

CX

CR

4; Il

10rb

; EPO

; TG

FB1;

IL23

A; C

CL1

6; V

EGFA

; CC

L13;

ifna

2;

TN

FRSF

10C

; TN

FRSF

17

0406

2 C

hem

okin

e si

gnal

ing

Org

anis

mal

Sys

tem

s;

0.02

0 83

JA

K3;

rac1

; Rap

1b; r

elA

; fox

o3b;

FO

XO

3; P

RK

CD

; Par

d3; A

DC

Y2;

PIK

3CG

;

path

way

Im

mun

e Sy

stem

N

FKB

1; C

CL1

4; C

CL1

5; R

hoa;

akt

1; S

HC

1; C

XC

L12;

AD

RB

K1;

PR

KA

CA

;

CX

CR

6; C

CR

2; C

CR

9; C

cl27

; CX

CR

3; W

AS;

Kra

s; C

CL4

L1; C

CL4

L2;

C

XC

L1; g

ng5;

SH

C2;

tiam

1; C

XC

R5;

Pik

3cb;

SH

C3;

PX

N; g

nb2;

GN

B1;

CC

R7;

RA

F1; L

OC

1001

2815

5; C

CL3

; DO

CK

2; N

FKB

IA; c

cr4;

ccl

1; C

xcl3

;

AD

CY

1; C

CL5

; SO

S1; P

IK3C

D; C

xcr1

; CC

L23;

CC

L22;

CR

KL;

Ccl

2; S

TAT1

;

PIK

3R3;

IL8;

gng

7; P

LCB

2; P

RK

CB

; CX

CR

4; a

kt2;

STA

T2; K

IAA

1549

;

CC

R1;

Sta

t5b;

CX

CL5

; CC

L16;

Sta

t3; C

CL1

3; C

dc42

; CD

C42

P2; R

asgr

p2;

C

XC

L2; i

kbkg

; XC

L2; W

ASL

; PIK

3R2;

CX

CR

2; g

nb3;

SO

S2

0407

0 Ph

osph

atid

ylin

osito

l En

viro

nmen

tal I

nfor

mat

ion

0.00

0 31

IT

PKA

; PIK

3CD

; PIK

3CG

; OC

RL;

CD

S1; C

alm

l3; P

IK3R

3; IT

PK1;

PIP

4K2B

;

sign

alin

g sy

stem

Pr

oces

sing

; Sig

nal

Prkc

a; P

I4K

B; P

LCG

2; IN

PP5A

; PLC

B2;

PR

KC

B; P

IP5K

1A; C

ALM

3;

Tran

sduc

tion

CA

LM2;

CA

LM1;

CA

LM3;

CA

LM2;

CA

LM1;

INPP

4A; P

ikfy

ve; P

RK

CG

;

Pik3

cb; I

TPR

1; P

IK3R

2; D

GK

Z; P

ip5k

1b; D

gkg

0411

5 p5

3 si

gnal

ing

path

way

C

ellu

lar P

roce

sses

; Cel

l 0.

006

34

Gad

d45g

; EI2

4; G

AD

D45

A; B

ID; C

CN

D1;

CY

CS;

mdm

2; M

DM

4; F

as;

Gro

wth

and

Dea

th

Apa

f1; T

hbs1

; LO

C65

1610

; ATM

; SER

PIN

B5;

LO

C64

8152

; LO

C65

1921

; ATR

;

CC

NB

2; C

dk6;

Gad

d45b

; GTS

E1; t

p53;

CC

ND

2; ig

fbp3

; CD

KN

1A; T

SC2;

CC

NG

2; B

AX

; SER

PIN

E1; I

gf1;

CA

SP8;

SFN

; rrm

2; S

IAH

1

0414

0 R

egul

atio

n of

aut

opha

gy

Cel

lula

r Pro

cess

es;

0.01

4 13

If

na14

; BEC

N1;

Ifna

10; I

FNA

6; G

AB

AR

AP;

ifna

2; G

AB

AR

APL

2; IF

NA

4;

Tr

ansp

ort a

nd C

atab

olis

m

IFN

A21

; GA

BA

RA

PL3;

GA

BA

RA

PL1;

IFN

A5;

Ulk

2

0415

0 m

TOR

sign

alin

g pa

thw

ay

Envi

ronm

enta

l Inf

orm

atio

n 0.

002

24

RPS

6KB

1; H

IF1A

; RPS

6P25

; RPS

6P1;

RPS

6; a

kt2;

KIA

A15

49; d

dit4

; EIF

4B;

Proc

essi

ng; S

igna

l

EI

F4B

P7; P

IK3C

D; R

PS6K

A2;

LO

C10

0127

984;

PIK

3CG

; TSC

2; V

EGFA

;

Tr

ansd

uctio

n

Ve

gfb;

PIK

3R3;

rheb

; Pik

3cb;

akt

1; Ig

f1; P

IK3R

2; U

lk2

0427

0 Va

scul

ar sm

ooth

mus

cle

Org

anis

mal

Sys

tem

s;

0.00

0 63

C

acna

1f; P

RK

CD

; Pla

2g2a

; prk

cq; A

DC

Y2;

Agt

r1; C

alm

l3; A

RH

GEF

12;

co

ntra

ctio

n C

ircul

ator

y Sy

stem

A

DR

A1A

; Rho

a; M

YLK

; PR

KA

CA

; LO

C40

7835

; Map

2k2;

Gna

13;

C

ALM

3; C

ALM

2; C

ALM

1; E

DN

RA

; CA

LM3;

CA

LM2;

CA

LM1;

PLA

2G1B

;

PTG

IR; P

RK

CG

; PLA

2G5;

PLA

2G10

; PPP

1R12

B; R

AM

P1; C

acna

1d;

AV

PR1B

; RA

F1; M

YH

11; A

DC

Y1;

Gna

s; P

pp1c

c; P

PP1R

12A

; MY

L6B

;

Ppp1

ca; P

rkca

; Prk

ce; a

cta2

; PLC

B2;

CA

CN

A1S

; NPR

1; C

YP4

A11

; PR

KC

B;

K

IAA

1549

; AD

RA

1D; A

RH

GEF

11; A

ctg2

; CA

LD1;

LO

C10

0131

098;

CA

CN

A1C

; Gna

12; I

TPR

1; G

UC

Y1A

3; a

dra1

b; G

NA

11; G

UC

Y1A

2; G

NA

Q;

K

CN

MA

1; M

YL9

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0431

0 W

nt si

gnal

ing

path

way

En

viro

nmen

tal I

nfor

mat

ion

0.00

0 59

C

AM

K2G

; rac

1; c

snk1

a1; C

CN

D1;

NFA

TC4;

btrc

; SFR

P4; R

hoa;

Ctb

p1;

Proc

essi

ng; S

igna

l

D

AA

M1;

map

k8; L

ef1;

WN

T2B

; PR

KA

CA

; CTB

P2; P

PP2C

B; P

PP2R

1A; t

p53;

Tran

sduc

tion

APC

2; n

fatc

1; C

TNN

B1;

NFA

T5; N

fatc

3; L

Y6G

5B; C

SNK

2B; C

hd8;

wnt

2;

pp

p3ca

; MY

C; J

un; P

RK

CG

; WN

T11;

Sfr

p1; S

KP1

; wnt

8b; F

bxw

11; t

bl1x

;

SIA

H1;

CSN

K1E

; MA

PK10

; FZD

7; sm

ad4;

chp

2; F

OSL

1; P

rkca

; MA

P3K

7;

PL

CB

2; P

PP2R

5C; P

RK

CB

; CC

ND

2; C

amk2

a; C

amk2

b; P

PP2C

A; p

pp2r

1b;

w

nt10

b; m

mp7

; SM

AD

3; P

PP3C

C; P

sen1

0434

0 H

edge

hog

sign

alin

g En

viro

nmen

tal I

nfor

mat

ion

0.00

1 17

C

SNK

1E; c

snk1

a1; B

MP6

; wnt

2; w

nt10

b; b

trc; I

HH

; BM

P5; Z

IC2;

Gli3

;

path

way

Pr

oces

sing

; Sig

nal

WN

T11;

CSN

K1D

; WN

T2B

; Fbx

w11

; wnt

8b; P

RK

AC

A; S

mo

Tran

sduc

tion

0435

0 TG

F-be

ta si

gnal

ing

Envi

ronm

enta

l Inf

orm

atio

n 0.

000

36

Inhb

b; A

CV

R1B

; thb

s4; B

MP6

; TN

F; tg

fbr1

; sm

ad4;

INH

BC

; Thb

s1; R

hoa;

pa

thw

ay

Proc

essi

ng; S

igna

l

e2

f4; i

d1; R

bl1;

LEF

TY2;

Id3;

RPS

6KB

1; L

tbp1

; IN

HB

A; P

PP2C

B; P

PP2R

1A;

Tran

sduc

tion

Tgfb

r2; T

GFB

1; G

DF5

; sp1

; ppp

2r1b

; PPP

2CA

; LEF

TY1;

MY

C; T

GFB

3;

B

MP5

; RB

L2; S

MA

D3;

SK

P1; E

2f5;

pitx

2; S

MA

D9

0436

0 A

xon

guid

ance

O

rgan

ism

al S

yste

ms;

0.

001

51

rac1

; eph

b1; N

FATC

4; S

EMA

4D; P

ak2;

AR

HG

EF12

; efn

a2; D

pysl

2; P

LXN

B3;

D

evel

opm

ent

Rho

a; E

FNA

5; C

XC

L12;

EFN

B2;

sem

a3f;

SEM

A3C

; AB

L1; n

fatc

1; N

FAT5

;

Nfa

tc3;

Slit

2; K

ras;

ppp

3ca;

EFN

A1;

EPH

B6;

RN

D1;

efn

b1; N

tng1

; Itg

b1; s

lit1;

Pak3

; EFN

A3;

SEM

A7A

; Efn

b3; c

hp2;

MET

; EPH

A4;

L1c

am; E

PHA

2;

C

XC

R4;

NC

K2;

Unc

5b; C

FL1;

SEM

A4F

; Eph

a5; e

phb2

; Cdc

42; C

DC

42P2

;

SEM

A5A

; PPP

3CC

; plx

nb2;

UN

C5C

0437

0 V

EGF

sign

alin

g En

viro

nmen

tal I

nfor

mat

ion

0.01

2 41

ra

c1; P

la2g

2a; P

IK3C

D; P

IK3C

G; m

apka

pk3;

NFA

TC4;

PIK

3R3;

Bad

; chp

2;

pa

thw

ay

Proc

essi

ng; S

igna

l

M

apk1

4; M

apk1

1; P

rkca

; akt

1; P

LCG

2; L

OC

4078

35; M

ap2k

2; P

RK

CB

;

Tr

ansd

uctio

n

PT

GS2

; MA

PKA

PK2;

akt

2; n

fatc

1; N

FAT5

; Nfa

tc3;

Kra

s; P

LA2G

1B; p

pp3c

a;

V

EGFA

; NO

S3; C

dc42

; CD

C42

P2; P

RK

CG

; SH

C2;

PLA

2G5;

PLA

2G10

;

Pik3

cb; P

PP3C

C; H

spb1

; HSP

BL2

; PX

N; P

IK3R

2; R

AF1

0451

0 Fo

cal a

dhes

ion

Cel

lula

r Pro

cess

es;

0.00

0 11

4 C

ol6a

3; R

ap1b

; FLN

B; I

TGA

5; it

ga6;

Pdg

fb; C

had;

CC

ND

1; P

IK3C

G;

Cel

l Com

mun

icat

ion

myl

2; A

CTG

1; B

CL2

; Rho

a; S

HC

1; m

apk8

; RA

SGR

F1; v

wf;

FLN

C; b

irc2;

C

TNN

B1;

MY

L12A

; MY

L12B

; CO

L11A

1; L

AM

A1;

PR

KC

G; S

HC

2; S

HC

3;

ca

v1; I

gf1;

CO

L6A

2; L

AM

C2;

CO

L1A

1; R

AF1

; Lam

a2; Z

YX

;

LOC

1001

2815

5; IB

SP; I

tgb1

; Itg

b5; M

APK

10; B

IRC

3; th

bs4;

Pak

3; S

OS1

;

PIK

3CD

; PPP

1R12

A; C

ol4a

6; C

RK

L; T

LN1;

LA

MA

4; P

IK3R

3; P

dgfr

b;

Pp

p1ca

; ITG

B3;

Thb

s1; P

rkca

; Hgf

; elk

1; F

LT1;

ITG

A9;

IGF1

R; l

amb2

;

KIA

A15

49; C

ol11

a2; V

egfb

; LA

MB

1; a

ctn4

; vcl

; CO

L6A

1; IT

GA

10; C

AV3;

rac1

; SPP

1; P

ak2;

Bad

; FLN

A; a

kt1;

MY

LK; a

ctn1

; CA

PN2;

LA

MC

1;

C

OL3

A1;

vtn

; Jun

; Pik

3cb;

LA

MA

5; A

CTB

; PX

N; i

tga2

b; p

dgfr

a; P

pp1c

c;

M

ET; I

LK; I

TGA

7; fn

1; T

NN

; PR

KC

B; I

tgav

; GR

LF1;

TLN

2; a

kt2;

CC

ND

2;

V

EGFA

; CO

L1A

2; C

dc42

; CD

C42

P2; I

TGA

3; T

NC

; col

4a2;

Col

4a1;

PIK

3R2;

SOS2

; Erb

b2; M

YL9

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0451

2 EC

M-r

ecep

tor

Envi

ronm

enta

l Inf

orm

atio

n 0.

000

54

Col

6a3;

ITG

A10

; ITG

A5;

sdc3

; itg

a6; C

had;

DA

G1;

SPP

1; G

P5; v

wf;

CD

47;

in

tera

ctio

n Pr

oces

sing

; Sig

nalin

g

LA

MC

1; C

OL3

A1;

CD

44; v

tn; H

spg2

; CO

L11A

1; L

AM

A1;

Sdc

4; L

AM

A5;

M

olec

ules

and

Inte

ract

ion

CO

L6A

2; L

AM

C2;

CO

L1A

1; L

ama2

; Itg

b1; G

P9; I

BSP

; HM

MR

; Itg

b5;

sd

c1; G

p1ba

; thb

s4; i

tga2

b; C

ol4a

6; L

AM

A4;

GP1

BB

; ITG

B3;

Thb

s1; I

TGA

7;

fn

1; T

NN

; ITG

A9;

Itga

v; la

mb2

; Col

11a2

; SV

2B; S

V2A

; CO

L1A

2; IT

GA

3;

TN

C; L

AM

B1;

col

4a2;

Col

4a1;

CO

L6A

1

0454

0 G

ap ju

nctio

n C

ellu

lar P

roce

sses

; 0.

003

39

Gna

s; A

DC

Y1;

Pdg

fb; p

dgfr

a; S

OS1

; AD

CY

2; T

UB

B2C

; GJA

1; D

RD

2; P

dgfr

b;

C

ell C

omm

unic

atio

n

H

TR2A

; Prk

ca; G

rm5;

PLC

B2;

PR

KA

CA

; Tub

b4; t

ubb2

b; P

RK

CB

;

LOC

4078

35; M

ap2k

2; T

UB

A4A

; LO

C39

9942

; TU

BA

1B; K

ras;

Tub

b2a;

Map

2k5;

PR

KC

G; I

TPR

1; G

UC

Y1A

3; G

RM

1; C

SNK

1D; M

C1R

; tub

b3; S

OS2

;

GN

A11

; RA

F1; G

UC

Y1A

2; G

NA

Q; T

UB

A3E

0461

0 C

ompl

emen

t and

O

rgan

ism

al S

yste

ms;

0.

000

31

fgb;

BD

KR

B2;

SER

PIN

G1;

kng

1; C

4BPA

; C8G

; PLA

UR

; CFH

; C1s

; Cd4

6;

coag

ulat

ion

casc

ades

Im

mun

e Sy

stem

FG

A; T

FPI;

vwf;

C6;

pro

C; F

3; se

rpin

d1; C

D59

; cfd

; mas

p2; p

lg; F

12; C

1QB

;

F7; S

ERPI

NE1

; CPB

2; C

1r; F

2; C

7; C

9; C

R1

0462

0 To

ll-lik

e re

cept

or

Org

anis

mal

Sys

tem

s;

0.02

3 49

N

FKB

IA; T

RA

F3; m

ap2k

6; ra

c1; M

APK

10; l

bp; r

elA

; IFN

A6;

CC

L5; I

KB

KE;

si

gnal

ing

path

way

Im

mun

e Sy

stem

PI

K3C

D; I

L6; P

IK3C

G; N

FKB

1; IL

1B; S

PP1;

STA

T1; T

NF;

PIK

3R3;

TLR

6;

IL

8; M

apk1

4; M

apk1

1; Ir

ak1;

akt

1; F

OS;

map

k8; M

AP3

K7;

IFN

A21

; IR

F5;

LO

C40

7835

; Map

2k2;

Ifna

14; I

fna1

0; a

kt2;

CC

L4L1

; CC

L4L2

; tab

2; IF

NA

4;

IF

NA

5; C

D80

; Jun

; RIP

K1;

ikbk

g; P

ik3c

b; if

na2;

PIK

3R2;

CA

SP8;

CC

L3

0462

2 R

IG-I

-like

rece

ptor

O

rgan

ism

al S

yste

ms;

0.

009

29

NFK

BIA

; TR

AF3

; MA

PK10

; IFN

A6;

relA

; DD

X3Y

; IK

BK

E; N

FKB

1; T

NF;

si

gnal

ing

path

way

Im

mun

e Sy

stem

IL

8; M

apk1

4; M

apk1

1; T

RIM

25; m

apk8

; MA

P3K

7; P

IN1;

IFN

A21

; SIK

E1;

If

na14

; Ifn

a10;

IFN

W1;

IFN

A4;

cas

p10;

IFN

A5;

RIP

K1;

ikbk

g; if

na2;

CA

SP8;

DD

X3X

0463

0 Ja

k-ST

AT si

gnal

ing

Envi

ronm

enta

l Inf

orm

atio

n 0.

012

67

JAK

3; JA

K1;

IL9R

; IFN

A6;

EPO

R; IF

NG

R2; I

L10R

A; O

SMR;

CCN

D1;

IL4;

path

way

Pr

oces

sing

; Sig

nal

PIK

3CG

; soc

s2; I

L6ST

; akt

1; C

SF3;

LEP

; IFN

A21

; Ifn

a10;

CSF

2RB;

Cbl

b;

Tran

sduc

tion

IFN

A5;

MY

C; L

EPR;

Soc

s1; P

ik3c

b; S

TAT4

; PIA

S1; c

sf3r

; gh2

; IFN

GR1

; Il5

;

TPO

; il1

0; IL

7R; S

OS1

; IL6

; PIK

3CD

; ZFP

91; C

NTF

; Zfp

91-C

ntf;

STAT

1; c

tf1;

PR

LR; P

IK3R

3; il

2rg;

Il5r

a; Il

10rb

; Ifn

a14;

Il24

; akt

2; C

CND

2; S

TAT2

; EPO

;

IFN

W1;

IFN

A4;

Sta

t5b;

IL13

; Il3

; IL2

3A; S

tat3

; LO

C344

593;

LO

C442

113;

PTPN

11; S

TAT6

; ifn

a2; P

IK3R

2; S

OS2

0464

0 H

emat

opoi

etic

cel

l O

rgan

ism

al S

yste

ms;

0.

018

53

csf1

; HLA

-DR

A; I

L9R

; LO

C65

2799

; LO

C65

3882

; KIT

; ITG

A5;

EPO

R; i

tga6

;

linea

ge

Imm

une

Syst

em

CD

33; I

L4; c

d38;

IL1B

; TN

F; G

P5; G

ypa;

CSF

3; C

D9;

Cd1

9; C

D44

; CD

59;

TF

RC

; CD

5; C

D3E

; CD

4; c

sf3r

; CD

1C; I

l1r1

; CD

22; G

P9; I

l5; T

PO; I

L7R

;

Gp1

ba; i

tga2

b; IL

6; C

d2; A

NPE

P; C

D8B

; GP1

BB

; ITG

AM

; ITG

B3;

CD

1A;

FC

ER2;

Il5r

a; C

D1D

; CD

34; E

PO; I

l3; I

TGA

3; M

S4A

1; C

R1;

FLT

3

0465

0 N

atur

al k

iller

cel

l O

rgan

ism

al S

yste

ms;

0.

016

64

SYK

; KIR

2DL4

; rac

1; IF

NA

6; IF

NG

R2;

FA

SLG

; LC

K; B

ID; P

IK3C

G;

m

edia

ted

cyto

toxi

city

Im

mun

e Sy

stem

N

FATC

4; T

NF;

SH

C1;

Ncr

1; P

LCG

2; P

rf1;

IFN

A21

; LO

C40

7835

; Map

2k2;

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

H

LA-G

; Ifn

a10;

nfa

tc1;

Nfa

tc3;

NFA

T5; K

ras;

ppp

3ca;

IFN

A5;

Sh3

bp2;

PRK

CG

; SH

C2;

HLA

-A; P

ik3c

b; S

HC

3; N

CR

3; R

AF1

; mic

B; L

OC

1001

2815

5;

IF

NG

R1;

TN

FSF1

0; K

LRK

1; S

OS1

; PIK

3CD

; PIK

3R3;

Fas

; FC

GR

3B; c

hp2;

Prkc

a; T

YR

OB

P; P

RK

CB

; Ifn

a14;

Cd2

47; I

CA

M1;

KIA

A15

49; I

FNA

4;

H

LA-E

; LO

C34

4593

; LO

C44

2113

; PTP

N11

; PPP

3CC

; ifn

a2; P

IK3R

2; S

OS2

;

KIR

3DS1

; Kir3

dl1;

TN

FRSF

10C

0466

0 T

cell

rece

ptor

O

rgan

ism

al S

yste

ms;

0.

020

56

relA

; LC

K; I

L4; p

rkcq

; PIK

3CG

; NFA

TC4;

NFK

B1;

TN

F; P

ak2;

Rho

a; a

kt1;

sign

alin

g pa

thw

ay

Imm

une

Syst

em

LOC

4078

35; M

ap2k

2; n

fatc

1; N

FAT5

; Nfa

tc3;

Cbl

b; K

ras;

ppp

3ca;

GR

AP2

;

CD

3E; P

dcd1

; Jun

; CD

4; P

ik3c

b; R

AF1

; LO

C10

0128

155;

NFK

BIA

; Il5

;

il10;

Pak

3; P

IK3C

D; S

OS1

; PIK

3R3;

CD

8B; C

D40

LG; c

hp2;

Map

k14;

Map

k11;

FO

S; T

EC; M

AP3

K7;

MA

LT1;

NC

K2;

Cd2

47; a

kt2;

Cdc

42;

C

DC

42P2

; Ptp

rc; i

kbkg

; PPP

3CC

; BC

L10;

LO

C64

6626

; PIK

3R2;

SO

S2; P

DK

1

0466

2 B

cel

l rec

epto

r O

rgan

ism

al S

yste

ms;

0.

011

45

NFK

BIA

; SY

K; r

ac1;

relA

; PIK

3CD

; SO

S1; P

IK3C

G; N

FATC

4; N

FKB

1;

si

gnal

ing

path

way

Im

mun

e Sy

stem

C

d79a

; PIK

3R3;

chp

2; F

OS;

akt

1; P

LCG

2; ra

sgrp

3; M

ALT

1; P

RK

CB

;

LOC

4078

35; M

ap2k

2; C

d19;

akt

2; C

d79b

; nfa

tc1;

NFA

T5; N

fatc

3; b

tk; K

ras;

ppp3

ca; F

cgr2

b; F

CG

R2C

; Jun

; CD

72; i

kbkg

; Ifit

m1;

Pik

3cb;

PPP

3CC

; CD

81;

B

CL1

0; L

OC

6466

26; P

IK3R

2; S

OS2

; CD

22; R

AF1

; LO

C10

0128

155

0466

4 Fc

eps

ilon

RI

Org

anis

mal

Sys

tem

s;

0.00

9 37

SY

K; I

l5; r

ac1;

map

2k6;

MA

PK10

; PR

KC

D; P

la2g

2a; I

L4; P

IK3C

D; S

OS1

;

sign

alin

g pa

thw

ay

Imm

une

Syst

em

PIK

3CG

; TN

F; P

IK3R

3; M

apk1

4; M

apk1

1; P

rkca

; akt

1; P

LCG

2; P

rkce

; map

k8;

PR

KC

B; L

OC

4078

35; M

ap2k

2; a

kt2;

btk

; Kra

s; P

LA2G

1B; I

L13;

Il3;

PLA

2G5;

PLA

2G10

; Pik

3cb;

PIK

3R2;

SO

S2; R

AF1

; PD

K1;

LO

C10

0128

155

0466

6 Fc

gam

ma

R-m

edia

ted

Org

anis

mal

Sys

tem

s;

0.00

3 43

SY

K; r

ac1;

PR

KC

D; P

PAP2

A; P

IK3C

D; P

IK3C

G; C

RK

L; G

sn; P

IK3R

3;

ph

agoc

ytos

is

Imm

une

Syst

em

ampH

; PIP

4K2B

; MA

RC

KSL

1; P

rkca

; akt

1; P

LCG

2; P

rkce

; MA

RC

KS;

PRK

CB

; PIP

5K1A

; RPS

6KB

1; a

kt2;

arp

c2; W

AS;

DN

M3;

CFL

1; W

asf2

;

Fcgr

2b; F

CG

R2C

; Cdc

42; C

DC

42P2

; Ptp

rc; P

ikfy

ve; P

RK

CG

; WA

SL; P

ik3c

b;

FC

GR

2A; P

IK3R

2; R

AF1

; Ppa

p2b;

Pip

5k1b

; AR

PC5;

LO

C10

0128

155;

DO

CK

2

0467

0 Le

ukoc

yte

Org

anis

mal

Sys

tem

s;

0.00

9 61

R

ap1b

; rac

1; N

cf4;

PIK

3CG

; AC

TG1;

myl

2; T

XK

; CLD

N3;

Rho

a; P

LCG

2;

tra

nsen

doth

elia

l Im

mun

e Sy

stem

C

tnna

1; C

XC

L12;

CTN

ND

1; a

ctn1

; Mm

p2; C

LDN

4; P

ECA

M1;

CTN

NB

1;

m

igra

tion

cl

dn18

; NO

X1;

MY

L12A

; MY

L12B

; EZR

; LO

C10

0129

652;

PR

KC

G; O

cln;

LOC

6478

59; P

ik3c

b; C

ldn8

; PX

N; A

CTB

; Rap

gef3

; LO

C10

0128

155;

Itgb1

; CLD

N10

; cld

n7; C

LDN

9; C

YB

B; P

IK3C

D; P

IK3R

3; M

apk1

4; m

sn;

IT

GA

M; M

apk1

1; P

rkca

; CX

CR

4; P

RK

CB

; GR

LF1;

Jam

3; IC

AM

1; C

dc42

;

CD

C42

P2; C

tnna

2; L

OC

3445

93; L

OC

4421

13; P

TPN

11; a

ctn4

; PIK

3R2;

vcl

;

MY

L9; C

D99

0472

0 Lo

ng-te

rm

Org

anis

mal

Sys

tem

s;

0.00

1 43

C

AM

K2G

; Rap

1b; A

DC

Y1;

ATF

4; A

TF4C

; Ppp

1cc;

PPP

1R12

A; C

alm

l3; c

hp2;

pote

ntia

tion

Ner

vous

Sys

tem

Pp

p1ca

; Prk

ca; G

rm5;

PLC

B2;

PR

KA

CA

; PR

KC

B; L

OC

4078

35; M

ap2k

2;

ca

mk4

; GR

IN2A

; CA

LM3;

CA

LM2;

CA

LM1;

KIA

A15

49; C

amk2

a; C

ALM

3;

C

ALM

2; C

ALM

1; C

amk2

b; K

ras;

RPS

6KA

2; L

OC

1001

2798

4; p

pp3c

a;

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

PR

KC

G; L

OC

1001

3109

8; C

AC

NA

1C; g

rin2c

; ITP

R1;

PPP

3CC

; GR

IA1;

GR

M1;

RA

F1; R

apge

f3; G

NA

Q

0472

2 N

euro

troph

in

Org

anis

mal

Sys

tem

s;

0.01

9 80

C

AM

K2G

; Rap

1b; r

ac1;

relA

; gab

1; fo

xo3b

; FO

XO

3; M

AG

ED1;

PR

KC

D;

si

gnal

ing

path

way

N

ervo

us S

yste

m

FASL

G; i

rs2;

PIK

3CG

; NFK

B1;

YW

HA

H; C

alm

l3; B

ad; B

CL2

; Rho

a; a

kt1;

SHC

1; P

LCG

2; m

apk8

; yw

haq;

LO

C40

7835

; Map

2k2;

cam

k4; A

BL1

;

MA

PKA

PK2;

tp53

; CA

LM3;

CA

LM2;

CA

LM1;

MA

P3K

5; C

ALM

3; C

ALM

2;

C

ALM

1; A

RH

GD

IA; K

ras;

RPS

6KA

2; L

OC

1001

2798

4; M

ap2k

5; Ju

n; S

HC

2;

Pi

k3cb

; BA

X; S

HC

3; R

AF1

; KID

INS2

20; N

FKB

IA; Y

WH

AZ;

MA

PK10

;

ATF4

; ATF

4C; S

OS1

; PIK

3CD

; CR

KL;

NTR

K3;

PIK

3R3;

YW

HA

B; N

TRK

1;

M

apk1

4; M

apk1

1; Ir

ak1;

akt

2; C

amk2

a; K

IAA

1549

; Cam

k2b;

LO

C44

0917

;

YW

HA

E; C

dc42

; CD

C42

P2; L

OC

3445

93; L

OC

4421

13; P

TPN

11; S

ort1

; Pse

n1;

N

TRK

2; P

IK3R

2; S

OS2

; PD

K1

0473

0 Lo

ng-te

rm d

epre

ssio

n O

rgan

ism

al S

yste

ms;

0.

003

36

Gna

s; P

la2g

2a; C

RH

R1;

NO

S2; P

rkca

; Grm

5; P

LCB

2; G

ria3;

PR

KC

B; G

na13

;

N

ervo

us S

yste

m

LOC

4078

35; M

ap2k

2; IG

F1R

; PPP

2CB

; PPP

2R1A

; KIA

A15

49; K

ras;

PLA

2G1B

; ppp

2r1b

; PPP

2CA

; NO

S3; P

RK

CG

; PLA

2G5;

Gna

12; P

LA2G

10;

IT

PR1;

GR

IA1;

Igf1

; GU

CY

1A3;

GR

M1;

GN

AZ;

GN

A11

; RA

F1; N

OS1

;

GU

CY

1A2;

GN

AQ

0474

0 O

lfact

ory

trans

duct

ion

Org

anis

mal

Sys

tem

s;

0.02

5 26

C

AM

K2G

; OR

2J2;

OR

1E1;

CA

LM3;

CA

LM2;

CA

LM1;

GU

CA

1A; O

R7E

24;

Sens

ory

Syst

em

Cam

k2a;

OR

2F2;

CA

LM3;

CA

LM2;

CA

LM1;

Cam

k2b;

CN

GB

1; O

R2H

2;

C

alm

l3; O

R2B

6; O

R10

H3;

OR

7A5;

GU

CA

1B; g

nal;

OR

5I1;

OR

2H1;

PRK

AC

A; P

de1c

0481

0 R

egul

atio

n of

act

in

Cel

lula

r Pro

cess

es;

0.00

0 10

5 pf

n2; I

QG

AP2

; ITG

A5;

itga

6; B

DK

RB

2; P

dgfb

; PIK

3CG

; AC

TG1;

myl

2; R

hoa;

cyto

skel

eton

C

ell M

otili

ty

NC

KA

P1; F

GF5

; LO

C40

7835

; Map

2k2;

APC

2; A

rhge

f7; W

AS;

FG

F18;

MY

L12A

; MY

L12B

; EZR

; LO

C10

0129

652;

Pik

fyve

; FG

F2; t

iam

1; F

gf3;

RA

F1; I

tgb1

; LO

C10

0128

155;

Itgb

5; P

ak3;

PIK

3CD

; SO

S1; P

PP1R

12A

;

CR

KL;

PIK

3R3;

ITG

AD

; Pdg

frb;

PIP

4K2B

; Ppp

1ca;

msn

; ITG

AM

; ITG

B3;

RR

AS2

; LO

C10

0133

211;

ITG

A9;

KIA

A15

49; C

FL1;

MY

H9;

FG

F4; W

ASL

;

F2; a

ctn4

; vcl

; FG

F8; r

dx; F

GF9

; pfn

1; IT

GA

10; r

ac1;

Gsn

; AR

HG

EF12

; Pak

2;

A

BI2

; MY

LK; a

ctn1

; Gna

13; C

YFI

P1; a

rpc2

; fgd

1; K

ras;

Pik

3cb;

PX

N; A

CTB

;

Pip5

k1b;

AR

PC5;

FG

FR2;

itga

2b; p

dgfr

a; P

pp1c

c; F

gfr1

; ITG

A7;

fn1;

PIP5

K1A

; Itg

av; G

RLF

1; IQ

GA

P1; R

ras;

Was

f2; I

TGA

3; C

dc42

; CD

C42

P2;

fg

f12;

Gna

12; T

MSL

1; T

MSB

4X; T

MSL

2; C

HR

M3;

PIK

3R2;

myh

10; S

OS2

;

Fgf7

; LO

C10

0132

771;

FG

F7P2

; MY

L9

0491

2 G

nRH

sign

alin

g O

rgan

ism

al S

yste

ms;

0.

003

53

CA

MK

2G; C

acna

1f; m

ap2k

6; M

APK

10; c

ga; A

DC

Y1;

Gna

s; P

RK

CD

; Pla

2g2a

;

path

way

En

docr

ine

Syst

em

ATF4

; ATF

4C; S

OS1

; AD

CY

2; C

alm

l3; M

apk1

4; M

apk1

1; P

rkca

; elk

1; m

apk8

;

MM

P14;

PLC

B2;

PR

KA

CA

; CA

CN

A1S

; PR

KC

B; L

OC

4078

35; M

ap2k

2;

M

mp2

; CA

LM3;

CA

LM2;

CA

LM1;

Cam

k2a;

CA

LM3;

CA

LM2;

CA

LM1;

Cam

k2b;

Kra

s; P

LA2G

1B; C

dc42

; CD

C42

P2; J

un; M

AP3

K4;

LO

C10

0131

098;

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

C

AC

NA

1C; P

LA2G

5; P

LA2G

10; I

TPR

1; C

acna

1d; F

SHB

; SO

S2; R

AF1

;

GN

A11

; GN

RH

2; G

NA

Q

0491

6 M

elan

ogen

esis

O

rgan

ism

al S

yste

ms;

0.

000

41

CA

MK

2G; L

OC

6527

99; L

OC

6538

82; K

IT; G

nas;

AD

CY

1; F

ZD7;

AD

CY

2;

En

docr

ine

Syst

em

CR

EB3L

2; P

OM

C; d

ct; C

alm

l3; C

REB

1; P

rkca

; Lef

1; ty

r; TY

RL;

PLC

B2;

W

NT2

B; P

RK

AC

A; L

OC

4078

35; M

ap2k

2; P

RK

CB

; CA

LM3;

CA

LM2;

CA

LM1;

CTN

NB

1; C

amk2

a; C

ALM

3; C

ALM

2; C

ALM

1; C

amk2

b; K

ras;

wnt

2; w

nt10

b; P

RK

CG

; WN

T11;

wnt

8b; R

AF1

; GN

AQ

;

0493

0 Ty

pe II

dia

bete

s H

uman

Dis

ease

s;

0.02

2 31

C

AC

NA

1G; M

APK

10; P

RK

CD

; PIK

3CD

; irs

2; S

LC2A

2; P

IK3C

G; T

NF;

mel

litus

M

etab

olic

Dis

ease

s

PI

K3R

3; so

cs2;

HK

3; P

rkce

; map

k8; A

BC

C8;

gck

; IN

SR; H

K2P

1; H

k2; P

KLR

;

CA

CN

A1E

; AD

IPO

Q; L

OC

1001

3109

8; C

AC

NA

1C; S

LC2A

4; P

ik3c

b; S

ocs1

;

Cac

na1d

; PIK

3R2;

pdx

1; L

OC

6527

97; P

KM

2; A

sip

0502

0 Pr

ion

dise

ases

H

uman

Dis

ease

s;

0.00

0 21

PR

NP;

LO

C40

0750

; HSP

A5;

CC

L5; H

SPA

1A; H

SPA

1B; I

L6; N

cam

1; IL

1B;

Neu

rode

gene

rativ

e

C

8G; C

1QB

; BA

X; e

lk1;

C7;

C9;

PR

KA

CA

; SO

D1;

C6;

LA

MC

1; L

OC

4078

35;

Dis

ease

s

M

ap2k

2

0520

0 Pa

thw

ays i

n ca

ncer

H

uman

Dis

ease

s;

0.00

0 17

4 C

DH

1; A

CV

R1B

; KLK

3; P

dgfb

; itg

a6; L

OC

1001

3297

3; T

CEB

1; C

CN

D1;

C

ance

rs

PIK

3CG

; NFK

B1;

NC

OA

4; B

CL2

; Rho

a; C

tbp1

; Ctn

na1;

PLC

G2;

map

k8;

fo

xo1;

WN

T2B

; CTB

P2; R

XR

G; H

DA

C2;

LO

C40

7835

; Map

2k2;

FG

F5; C

dk6;

AB

L1; b

irc2;

E2F

1; tp

53; T

gfbr

2; A

PC2;

CTN

NB

1; F

GF1

8; b

cr; C

DK

N1A

;

Cbl

b; M

YC

; TG

FB3;

NO

S3; L

AM

A1;

PR

KC

G; F

GF2

; WN

T11;

Igf1

; Fgf

3;

cs

f3r;

LAM

C2;

wnt

8b; C

ASP

8; N

OS1

; RA

F1; L

ama2

; Itg

b1; S

mo;

ZB

TB16

;

Hsp

90b1

; NFK

BIA

; MA

PK10

; RET

; BIR

C3;

SO

S1; P

IK3C

D; C

ol4a

6; M

sh2;

NFK

B2;

CR

KL;

PIK

3R3;

LA

MA

4; F

as; P

dgfr

b; IL

8; F

OS;

Prk

ca; H

gf;

H

SP90

AA

2; H

SP90

AA

1; T

PM3;

RB

1; H

IF1A

; IG

F1R

; lam

b2; K

IAA

1549

;

vhl;

Stat

5b; C

DK

N1B

; Veg

fb; E

TS1;

FG

F4; C

tnna

2; E

2f2;

Ar;

LAM

B1;

GST

P1; B

rca2

; RX

RA

; FG

F8; F

LT3;

FG

F9; J

AK

1; ra

c1; T

raf1

; LO

C65

2799

;

LOC

6538

82; K

IT; r

elA

; FA

SLG

; TG

FA; N

OS2

; BID

; RA

LGD

S; C

YC

S; m

dm2;

Tceb

2; B

ad; R

ALB

P1; L

OC

1001

2977

3; a

kt1;

Run

x1; L

ef1;

LA

MC

1; M

mp2

;

Skp2

; Kra

s; w

nt2;

Jun;

BA

X; P

ik3c

b; G

li3; P

IAS1

; LA

MA

5; P

AX

8; T

RA

F3;

FG

FR2;

pdg

fra;

itga

2b; I

L6; F

ZD7;

HSP

90A

B1;

STA

T1; t

gfbr

1; N

TRK

1;

sm

ad4;

AR

NT;

MET

; Fgf

r1; f

n1; P

RK

CB

; MA

X; P

TGS2

; CC

NA

1; It

gav;

akt

2;

TG

FB1;

wnt

10b;

Sta

t3; V

EGFA

; fgf

12; C

dc42

; CD

C42

P2; I

TGA

3; ik

bkg;

Hda

c1; F

H; c

ol4a

2; S

MA

D3;

Col

4a1;

RU

NX

1T1;

PIK

3R2;

SO

S2; E

rbb2

; Fgf

7;

LO

C10

0132

771;

FG

F7P2

0521

0 C

olor

ecta

l can

cer

Hum

an D

isea

ses;

0.

003

41

rac1

; MA

PK10

; AC

VR

1B; p

dgfr

a; C

CN

D1;

RA

LGD

S; S

OS1

; PIK

3CD

; FZD

7;

Can

cers

PI

K3C

G; C

YC

S; M

sh2;

tgfb

r1; P

IK3R

3; P

dgfr

b; sm

ad4;

Bad

; BC

L2; F

OS;

akt1

; MET

; map

k8; L

ef1;

IGF1

R; a

kt2;

tp53

; APC

2; T

gfbr

2; T

GFB

1;

K

IAA

1549

; CTN

NB

1; K

ras;

MY

C; T

GFB

3; Ju

n; B

AX

; Pik

3cb;

SM

AD

3;

PI

K3R

2; S

OS2

; RA

F1

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0521

1 R

enal

cel

l car

cino

ma

Hum

an D

isea

ses;

0.

015

42

rac1

; Rap

1b; g

ab1;

Pdg

fb; T

GFA

; LO

C10

0132

973;

TC

EB1;

Pak

3; P

IK3C

D;

Can

cers

SO

S1; P

IK3C

G; C

RK

L; P

IK3R

3; P

ak2;

Tce

b2; A

RN

T; a

kt1;

MET

; Hgf

;

LOC

4078

35; M

ap2k

2; H

IF1A

; akt

2; T

GFB

1; K

IAA

1549

; vhl

; Kra

s; V

EGFA

;

TGFB

3; V

egfb

; Cdc

42; C

DC

42P2

; ETS

1; Ju

n; L

OC

3445

93; L

OC

4421

13;

PT

PN11

; FH

; Pik

3cb;

PIK

3R2;

SO

S2; R

AF1

0521

2 Pa

ncre

atic

can

cer

Hum

an D

isea

ses;

0.

000

43

JAK

1; ra

c1; M

APK

10; r

elA

; AC

VR

1B; T

GFA

; CC

ND

1; R

ALG

DS;

PIK

3CD

;

C

ance

rs

PIK

3CG

; NFK

B1;

STA

T1; t

gfbr

1; P

IK3R

3; sm

ad4;

RA

LBP1

; LO

C10

0129

773;

Bad

; akt

1; m

apk8

; RB

1; C

dk6;

E2F

1; a

kt2;

tp53

; TG

FB1;

Tgf

br2;

KIA

A15

49;

K

ras;

VEG

FA; T

GFB

3; V

egfb

; Sta

t3; C

dc42

; CD

C42

P2; E

2f2;

ikbk

g; P

ik3c

b;

SM

AD

3; B

rca2

; PIK

3R2;

RA

F1; E

rbb2

0521

4 G

liom

a H

uman

Dis

ease

s;

0.00

1 45

C

AM

K2G

; TG

FA; P

dgfb

; pdg

fra;

CC

ND

1; P

IK3C

D; S

OS1

; PIK

3CG

; mdm

2;

Can

cers

C

alm

l3; P

IK3R

3; P

dgfr

b; P

rkca

; akt

1; S

HC

1; P

LCG

2; R

B1;

PR

KC

B;

LO

C40

7835

; Map

2k2;

Cdk

6; IG

F1R

; E2F

1; C

ALM

3; C

ALM

2; C

ALM

1; a

kt2;

tp53

; KIA

A15

49; C

amk2

a; C

ALM

3; C

ALM

2; C

ALM

1; C

amk2

b; K

ras;

CD

KN

1A; P

RK

CG

; E2f

2; S

HC

2; P

ik3c

b; S

HC

3; Ig

f1; P

IK3R

2; S

OS2

; RA

F1

0521

5 Pr

osta

te c

ance

r H

uman

Dis

ease

s;

0.00

0 51

N

FKB

IA; r

elA

; KLK

3; F

GFR

2; T

GFA

; Pdg

fb; A

TF4;

ATF

4C; p

dgfr

a; C

CN

D1;

C

ance

rs

SOS1

; PIK

3CD

; PIK

3CG

; mdm

2; N

FKB

1; C

REB

3L2;

HSP

90A

B1;

CR

EB1;

PIK

3R3;

Pdg

frb;

Bad

; BC

L2; a

kt1;

Lef

1; fo

xo1;

Fgf

r1; H

SP90

AA

2;

H

SP90

AA

1; R

B1;

LO

C40

7835

; Map

2k2;

IGF1

R; E

2F1;

akt

2; tp

53; K

IAA

1549

;

CTN

NB

1; K

ras;

CD

KN

1A; C

DK

N1B

; E2f

2; ik

bkg;

Ar;

Pik3

cb; G

STP1

; Igf

1;

PI

K3R

2; S

OS2

; RA

F1; E

rbb2

; Hsp

90b1

0521

7 B

asal

cel

l car

cino

ma

Hum

an D

isea

ses;

0.

008

12

tp53

; Gli3

; APC

2; W

NT1

1; C

TNN

B1;

Lef

1; F

ZD7;

WN

T2B

; wnt

8b; w

nt10

b;

C

ance

rs

wnt

2; S

mo

0521

8 M

elan

oma

Hum

an D

isea

ses;

0.

001

41

FGF9

; CD

H1;

Pdg

fb; p

dgfr

a; C

CN

D1;

PIK

3CD

; PIK

3CG

; mdm

2; P

IK3R

3;

Can

cers

Pd

gfrb

; Bad

; akt

1; M

ET; H

gf; F

gfr1

; RB

1; F

GF5

; LO

C40

7835

; Map

2k2;

Cdk

6;

IG

F1R

; E2F

1; a

kt2;

tp53

; KIA

A15

49; F

GF1

8; K

ras;

CD

KN

1A; f

gf12

; FG

F4;

E2

f2; F

GF2

; Pik

3cb;

Fgf

3; Ig

f1; P

IK3R

2; R

AF1

; FG

F8; F

gf7;

LO

C10

0132

771;

FGF7

P2

0521

9 Bl

adde

r can

cer

Hum

an D

iseas

es;

0.00

2 20

CD

H1;

E2F

1; tp

53; K

IAA

1549

; CCN

D1;

CD

KN

1A; K

ras;

mdm

2; M

YC;

VEG

FA;

Canc

ers

Vegf

b; E

2f2;

IL8;

Thb

s1; R

AF1

; RB

1; M

mp2

; LO

C40

7835

; Map

2k2;

Erb

b2

0522

0 C

hron

ic m

yelo

id

Hum

an D

isea

ses;

0.

003

52

relA

; AC

VR

1B; C

CN

D1;

PIK

3CG

; mdm

2; N

FKB

1; B

ad; C

tbp1

; Run

x1; a

kt1;

leuk

emia

C

ance

rs

SHC

1; C

TBP2

; HD

AC

2; L

OC

4078

35; M

ap2k

2; C

dk6;

AB

L1; E

2F1;

tp53

;

Tgfb

r2; b

cr; C

blb;

CD

KN

1A; K

ras;

MY

C; T

GFB

3; S

HC

2; P

ik3c

b; S

HC

3;

R

AF1

; NFK

BIA

; PIK

3CD

; SO

S1; C

RK

L; tg

fbr1

; PIK

3R3;

smad

4; R

B1;

akt

2;

TG

FB1;

KIA

A15

49; S

tat5

b; C

DK

N1B

; Hda

c1; L

OC

3445

93; L

OC

4421

13;

PT

PN11

; ikb

kg; E

2f2;

SM

AD

3; P

IK3R

2; S

OS2

Add

ition

al T

able

6B

. Con

tinue

d.

Cot

inue

d on

nex

t the

pag

e



thw

ay

Path

way

nam

es

Cla

ssifi

catio

n P

valu

e N

umbe

r of g

enes

In

clud

ed g

enes

entry

expr

esse

d in

the

path

way

s

0522

1 A

cute

mye

loid

H

uman

Dis

ease

s;

0.01

4 33

LO

C65

2799

; LO

C65

3882

; KIT

; rel

A; C

CN

D1;

PIK

3CD

; SO

S1; P

IK3C

G;

le

ukem

ia

Can

cers

N

FKB

1; P

IK3R

3; B

ad; R

unx1

; akt

1; L

ef1;

LO

C40

7835

; Map

2k2;

RPS

6KB

1;

C

CN

A1;

akt

2; K

IAA

1549

; Kra

s; P

im2;

Sta

t5b;

MY

C; S

tat3

; ikb

kg; P

ik3c

b;

R

UN

X1T

1; P

IK3R

2; S

OS2

; RA

F1; Z

BTB

16; F

LT3

0522

2 Sm

all c

ell l

ung

Hum

an D

isea

ses;

0.

000

53

Traf

1; re

lA; i

tga6

; NO

S2; C

CN

D1;

PIK

3CG

; CY

CS;

NFK

B1;

BC

L2; A

paf1

;

canc

er

Can

cers

ak

t1; L

AM

C1;

RX

RG

; Skp

2; C

dk6;

birc

2; E

2F1;

tp53

; MY

C; N

OS3

; LA

MA

1;

Pi

k3cb

; PIA

S1; L

AM

A5;

LA

MC

2; N

OS1

; Lam

a2; I

tgb1

; NFK

BIA

; TR

AF3

;

BIR

C3;

itga

2b; P

IK3C

D; C

ol4a

6; P

IK3R

3; L

AM

A4;

fn1;

RB

1; M

AX

; PTG

S2;

Itg

av; a

kt2;

lam

b2; C

DK

N1B

; ITG

A3;

FH

IT; E

2f2;

ikbk

g; L

AM

B1;

col

4a2;

RX

RA

; Col

4a1;

PIK

3R2

0522

3 N

on-s

mal

l cel

l lun

g H

uman

Dis

ease

s;

0.00

2 32

fo

xo3b

; FO

XO

3; T

GFA

; CC

ND

1; P

IK3C

D; S

OS1

; PIK

3CG

; PIK

3R3;

Bad

;

canc

er

Can

cers

Pr

kca;

akt

1; P

LCG

2; R

XR

G; R

B1;

LO

C40

7835

; Map

2k2;

PR

KC

B; C

dk6;

E2F1

; akt

2; tp

53; K

IAA

1549

; Kra

s; F

HIT

; PR

KC

G; E

2f2;

Pik

3cb;

RX

RA

;

PIK

3R2;

RA

F1; S

OS2

; Erb

b2

0531

0 A

sthm

a H

uman

Dis

ease

s; Im

mun

e 0.

023

16

Il5; H

LA-D

OB

; HLA

-DR

A; R

NA

SE3;

il10

; HLA

-DQ

B1;

LO

C10

0133

583;

Syst

em D

isea

ses

IL4;

IL13

; Il3

; TN

F; C

D40

LG; E

PX; h

la-d

pa1;

HLA

-DPB

1; H

LA-D

OA

0532

0 A

utoi

mm

une

thyr

oid

Hum

an D

isea

ses;

Imm

une

0.01

7 30

Il5

; HLA

-DO

B; T

PO; H

LA-D

RA

; IFN

A6;

cga

; il1

0; F

ASL

G; H

LA-D

QB

1;

di

seas

e Sy

stem

Dis

ease

s

LO

C10

0133

583;

IL4;

Tsh

b; F

as; C

D40

LG; T

SHR

; hla

-dpa

1; P

rf1;

IFN

A21

;

HLA

-DPB

1; H

LA-G

; Ifn

a14;

Ifna

10; I

FNA

4; IF

NA

5; C

D80

; HLA

-E; H

LA-A

;

ifna2

; HLA

-F; H

LA-D

OA

0534

0 Pr

imar

y H

uman

Dis

ease

s; Im

mun

e 0.

013

19

Cd1

9; JA

K3;

Rag

2; C

iita;

RA

G1;

rfxa

nk; I

L7R

; LC

K; T

AP2

; btk

; ada

;

imm

unod

efici

ency

Sy

stem

Dis

ease

s

C

d79a

; CD

3E; P

tprc

; CD

8B; C

D40

LG; i

kbkg

; il2

rg; C

D4

0541

0 H

yper

troph

ic

Hum

an D

isea

ses;

0.

000

49

ITG

A10

; Itg

b5; C

acna

1f; I

TGA

5; it

ga6;

MY

BPC

3; it

ga2b

; lm

na; A

TP2A

2; IL

6;

ca

rdio

myo

path

y (H

CM

) C

ardi

ovas

cula

r Dis

ease

s

D

AG

1; m

yl2;

AC

TG1;

dm

d; T

NF;

LO

C64

3634

; CA

CN

B4;

ITG

B3;

CA

CN

B1;

Myl

3; S

GC

A; I

TGA

7; C

AC

NA

1S; T

PM3;

CA

CN

B2;

tpm

2; IT

GA

9; It

gav;

Myh

7; D

ES; T

PM1;

PR

KA

B2;

TG

FB1;

TTN

; TG

FB3;

ITG

A3;

Act

c1;

LO

C10

0131

098;

CA

CN

A1C

; Cac

na2d

1; sg

cg; I

gf1;

Cac

na1d

; CA

CN

G3;

AC

TB; C

AC

NG

1; L

ama2

; Itg

b1; S

LC8A

1

0541

2 A

rrhy

thm

ogen

ic ri

ght

Hum

an D

isea

ses;

0.

000

41

ITG

A10

; Itg

b5; C

acna

1f; I

TGA

5; it

ga6;

itga

2b; A

TP2A

2; lm

na; D

AG

1; A

CTG

1;

ve

ntric

ular

C

ardi

ovas

cula

r Dis

ease

s

G

JA1;

dm

d; C

AC

NB

4; IT

GB

3; C

AC

NB

1; C

tnna

1; S

GC

A; L

ef1;

act

n1; I

TGA

7;

ca

rdio

myo

path

y (A

RVC

)

CA

CN

A1S

; CA

CN

B2;

ITG

A9;

Itga

v; D

ES; C

TNN

B1;

ITG

A3;

Ctn

na2;

LOC

1001

3109

8; C

AC

NA

1C; C

acna

2d1;

sgcg

; CA

CN

G3;

Cac

na1d

; AC

TB;

C

AC

NG

1; a

ctn4

; dsp

; Lam

a2; I

tgb1

; SLC

8A1

Add

ition

al T

able

6B

. Con

tinue

d.

Documents

Key pathways involved in prostate cancer based on gene set ... · The major challenge for genome-wide RNA expression analysis is not to obtain gene expression profiles, but to extract