Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A)...

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Supplementary Figure 1A HNF4A WNT5A VANGL1 PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1. (B) The expression pattern of the four genes (HNF4A, VANGL1, WNT5A, PLCB1) in various datasets (166 datasets) reported by ArrayExpress. We extracted the expressions of the four genes from ArrayExpress and generated the heatmap by using matrix2png program.

Transcript of Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A)...

Page 1: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

Supplementary Figure 1A

HNF4AWNT5AVANGL1PCLB1

Supplementary Figure 1B

Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1. (B) The expression pattern of the four genes (HNF4A, VANGL1, WNT5A, PLCB1) in various datasets (166 datasets) reported by ArrayExpress. We extracted the expressions of the four genes from ArrayExpress and generated the heatmap by using matrix2png program.

Page 2: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

Supplementary Figure 2

Supplementary Figure 2. Example of the selection step of PATHOME. (A) Assumed subpathway toy that consists of 6 nodes and 5 edges. According to our index notation, p is 6 and i 1 to 5. Blunt-ended edge indicates inhibition and arrow-headed edge activation. In each group, nominal values of rk

i,i+1s were given by the table for the following explanation. (B) Following our notation, edges (ei,i+1s) were coded by -1, +1, -1, +1, and +1, from left to right, respectively. Subsequently, we showed how the curly bracket (say yk; k: group index) of the lk (the length of the segment) equation was calculated. The graphs of yk (k=1,2) versus m (1 to 5) indicate that arguments minimizing yks are 4 and 5 for group 1 and group 2, respectively. Thus, l1 and l2 are 5 and 6, respectively. l1 and l2 are considered in the test step of PATHOME.

Page 3: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

Supplementary Figure 3

Supplementary Figure 3. Measurement of expression level by RT-PCR, WNT5A, VANGL1, FZD1 and PLCB1, in the gastric cancer cell line panels.

Page 4: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

KEGG identifier Description Entries in the significant subpathways belonging to the pathwayhsa04930 Type II diabetes mellitus PIK3R5,PIK3R3,IRS2,PIK3CB,SLC2A4,MAPK1hsa05218 Melanoma IGF1,PDGFC,RAF1,CCND1,NRAS,FGF7,MAPK3,FGF11,MAP2K2,FGF13,FGF2,EGFR,PDGFRB

,PDGFA,IGF1R,PDGFRA,FGF9,FGF3,PDGFDhsa04650 Natural killer cell mediated

cytotoxicityPLCG1,PPP3CB,TNFSF10,IFNGR2,TNFRSF10A,TNFRSF10D,IFNAR1,NFATC1,IFNA8,IFNG,BRAF,CSF2,MAPK1,MAP2K1,TNF

hsa04062 Chemokine signaling pathway

GSK3A,XCL1,NFKBIA,PTK2,CXCL10,CCL21,GNB5,CCL8,CCL26,CCR10,ARRB2,CXCR4,WASL,GRK7,CXCL14,ITK,CCL4L1,CCL11,CXCL3,CCL3L1,PAK1,ADCY7,GNG5,CCL5,CCL23,PRKACB,GNG2,FOXO3,CSK,CX3CR1,PIK3CB,CXCL12,GNGT2,PXN,GNG10,PLCB2,PIK3CD,CX3CL1,FGR,GNAI3,CCR2,PRKCZ,CCL3,CXCL9,CCL18,PTK2B,CCR6,PIK3R2,MAPK3,PLCB3,CXCL16,CRK,CXCL13,GNB2,PPBP,CCR1,CXCR1,CXCL5,GNAI2,IL8,CCL22,LYN,BRAF,GNG12,AKT1,PIK3R1,JAK2,CXCL1,CXCL6,GSK3B,GRK6,GNGT1,PIK3R5,AKT3,STAT3,MAPK1,CCR5,ADCY2,CCL20,CCL2,CCL1,CCL7,CCL4L2,PRKACA,PRKCD,CCR9,GRK5,CCL3L3,CXCL11,PRKACG,STAT1,GRK1,GNG3,ADCY6,PRKX,VAV1,PIK3CG,CCL24,NRAS,NCF1,BCAR1,CCL17,CCL19,CXCL2,GNG4,AKT2,GNAI1,MAP2K1,NFKB1,CCL25,IKBKB,CCR7,PF4V1,XCL2,GNG11,CDC42,CCL15,GNG7,GNB1,CXCR6,CXCR3,PIK3CA,GNB3,ADRBK2,CCL4,PF4,PIK3R3,CCR4,CCL13,CXCR5,CCL27,ARRB1

hsa04912 GnRH signaling pathway GNA11,CAMK2A,PLA2G6,PRKCA,PLCB3,GNRHR,CALM2,ITPR3,PLD1,CAMK2D,CALML6,CAMK2G,ITPR1,CALML5,PLCB1,PLCB4

hsa05213 Endometrial cancer PDPK1,EGF,PIK3CB,CASP9,AKT2,EGFRhsa04114 Oocyte meiosis ITPR3,CDC16,PPP3CB,CCNB1,CALML6,CALML5,PPP3CC,ANAPC4,ITPR1,ANAPC5hsa04666 Fc gamma R-mediated

phagocytosisPIK3CB,PLCG1,LYN,PLA2G6,PTPRC,PRKCD,GAB2,DNM3

hsa04810 Regulation of actin cytoskeleton

ITGA1,ITGB1,ITGA6,CFL2,RAC1,ITGA11,ITGB6,PAK1,ITGB5,BAIAP2,ITGA2,CRK,DOCK1,ITGB4,WASF2,LIMK2,ARPC1B,ARPC1A,ITGAD,ITGA2B,ARPC2,ITGAV,ITGA9

hsa04910 Insulin signaling pathway INSR,PTPN1,HK3,PDE3A,PIK3R3,IRS2,PIK3CB,PRKCI,SREBF1,PDPK1,PIK3R5,PIK3CA,AKT2hsa05221 Acute myeloid leukemia PIK3R3,CHUK,SOS1,RELA,NRAS,PIK3R5,PIK3CA,FLT3,AKT2,GRB2hsa04710 Circadian rhythm - mammal CLOCK,CRY1,ARNTL,NR1D1hsa04630 Jak-STAT signaling pathway IL6ST,SOCS4,IL9R,CBLC,IL7R,STAT6,STAT5A,PIAS4,CRLF2,IL28RA,OSMR,IL22RA2,PTPN6,C

SF2RB,GHR,LEPR,IL22RA1,AKT2,AKT1,IL2RB,STAM2,IL12RB1,PIK3R1,JAK2,IL6R,LIFR,IL20RB,TYK2,CBL,PIK3R5,IL10RA,AKT3,IL15RA,SOCS7,STAT3,SOCS2,MYC,MPL,CREBBP,STAT4,CCND1,IL3RA,IRF9,PIK3R2,PIK3CA,CBLB,PIAS2,SOCS1,IL2RA,PIM1,IFNAR2,IL13RA1,STAT5B,IL23R,PIAS3,STAT1,PIK3R3,SOCS5,JAK3,PIK3CB,EP300,IFNGR2,PTPN11,JAK1,CSF2RA

hsa04664 Fc epsilon RI signaling pathway

MAPK9,RAC1,MAP2K4,VAV2

hsa05120 Epithelial cell signaling in Helicobacter pylori infection

NFKB1,NFKBIA,IKBKB,CCL5

hsa05142 Chagas disease JUN,MAPK12,IRAK4,TLR9,MAP2K4,MAPK10,FOS,TRAF6,MYD88hsa05215 Prostate cancer IGF1,PDGFC,INSRR,PIK3R2,PIK3CA,AKT2,EGFR,PDGFB,PDGFRB,PIK3R3,PDGFA,EGF,IGF1R,

PIK3CB,CASP9,PDGFRA,TGFA,PIK3R5,PDPK1,PDGFD,FGFR1,AKT3,ERBB2,INS,FOXO1hsa05200 Pathways in cancer PGF,NFKB2,VEGFA,CDK4,NFKBIA,BRAF,MAP2K1,EGFR,MMP1,STAT1,BIRC3,IKBKB,EGF,JA

K1,TGFA,IL8,MYC,MAPK1hsa04510 Focal adhesion ACTB,ITGA6,MYLPF,ITGA3,BIRC2,CCND1,PAK2,BCAR1,ELK1,PIK3CA,RAC1,PTK2,CRK,XIAP,

ITGA2,MAP2K1,DOCK1,PAK6,ITGB4,PIK3R3,PAK4,PIK3CB,PDGFRA,PIK3R5,MAPK1,ITGA9,PXN,MYLK,ILK,ITGA10

hsa04010 MAPK signaling pathway RPS6KA6,PTPN7,PLA2G12B,RAF1,STMN1,PLA2G6,NRAS,MAPK3,RASA2,MAP2K2,CACNA2D3,BRAF,MOS,MAP2K1,CACNA2D2,PLA2G3,RASGRF1,PLA2G1B,RRAS,RASGRP1,CACNA1C,CACNA1H,CACNA1S,CACNB4,ATF4,MRAS,RPS6KA2,MAPK1,RASGRP3

hsa05100 Bacterial invasion of epithelial cells

WASL,ACTB,CBLC,PIK3CA,RAC1,CRK,GAB1,DOCK1,ARPC4,WASF2,PIK3CB,ARPC3,ARPC1B,ACTG1,CBL,ARPC1A,ARPC2,PIK3R5,MET,CDC42

hsa04920 Adipocytokine signaling pathway

PRKAA1,PRKAB2,ADIPOR1,LEPR,SLC2A4,CAMKK2,STK11

hsa04310 Wnt signaling pathway PPARD,NLK,WNT2B,FZD4,CSNK1A1L,CSNK2A1,DVL1,CTNNB1,CCND2,CER1,WNT9A,NFATC4,WNT6,DVL2,CSNK2A2,MAP3K7,CAMK2D,AXIN2,SFRP1,PLCB1,PLCB4,MYC,FZD10,FZD2,DVL3,CCND1,PRKCA,PPP3CC,NFATC1,TCF7L2,PRKACB,FZD3,CCND3,PORCN,FZD8,WNT5A,FZD5,WNT2,PPP3CB,CSNK1A1,MMP7,FZD6,PRKX,WNT10B,WNT4,CSNK2B,PRKCG,TCF7,PSEN1,CAMK2B

hsa04722 Neurotrophin signaling pathway

SH2B3,SHC1,BDNF,PLCG1,RAF1,SOS1,NTRK3,NRAS,MAPK3,SH2B1,PRKCD,MAP2K2,AKT2,NTRK2,NTF3,PIK3R3,FOXO3,PIK3CB,SHC3,CAMK2D,PTPN11,ATF4,PIK3R5,CALML5,RPS6KA2,GRB2

hsa05223 Non-small cell lung cancer EGF,PIK3CB,CASP9,TGFA,PDPK1,PIK3CA,ERBB2,AKT2,EGFRhsa04360 Axon guidance SEMA4F,EPHA2,PAK3,CDK5,PAK7,NGEF,PLXNA2,PLXNB1,EFNA1,SEMA4G,RHOD,RAC2,DP

YSL2,EFNA4hsa05131 Shigellosis ARPC5,WASL,VCL,PFN3

Supplementary Table 1. The 27 KEGG pathways containing the significant 113,810 subpathways in GSE13861 (FDR < 0.05). For the comparison, all the significant subpathways were assigned to their pathways.

Page 5: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

KEGG identifer:descrption

P-Value Genes Fold Enrichment

Benjamini FDR (%)

hsa00980:Metabolism of xenobiotics by cytochrome P450

1.18E-10 GSTA1, GSTA2, CYP3A5, GSTA4, CYP2C18, CYP2C9, CYP2S1, ADH1C, GSTT1, ADH1B, ADH1A, ADH7, ALDH3A1, AKR1C3, GSTM2, AKR1C2, UGT2B17, GSTM3, AKR1C4, UGT2B10, UGT2B15, UGT2B7

6.163636364 1.87E-08 1.42E-07

hsa00982:Drug metabolism 1.37E-08 GSTA1, GSTA2, CYP3A5, GSTA4, CYP2C18, CYP2C9, MAOA, ADH1C, GSTT1, ADH1B, ADH1A, ADH7, ALDH3A1, GSTM2, FMO5, UGT2B17, GSTM3, UGT2B10, UGT2B15, UGT2B7

5.368328446 1.08E-06 1.65E-05

hsa04512:ECM-receptor interaction

3.26E-05 COL4A2, COL4A1, COL3A1, COL5A2, COL4A6, CD36, ITGB7, COL6A3, COL1A2, LAMC2, AGRN, COL1A1, COL11A1, THBS2, SPP1, THBS4

3.522077922 0.001716658 0.039299251

hsa00830:Retinol metabolism 1.09E-04 CYP3A5, CYP2C9, CYP2C18, ADH1C, ADH1B, DHRS9, ADH1A, ADH7, RDH12, ALDH1A1, UGT2B17, UGT2B10, UGT2B15, UGT2B7

4.109090909 0.004306259 0.131553541

hsa04060:Cytokine-cytokine receptor interaction

0.003434127

CXCL1, TNFRSF6B, IL1R2, TNFRSF12A, LEPR, KIT, CXCL6, IL7R, CXCL12, TNFRSF11B, CXCR5, CXCR6, IL1B, CD27, GHR, IL18RAP, IL8, TNFRSF13B, LIFR, TNFRSF17, CCL15, IL11RA, CCR7, TNFSF11, CXCL14, PDGFRB

1.834975711 0.10300516 4.060151471

hsa00480:Glutathione metabolism

0.00477074

GSTA1, GSTM2, GSTA2, GSTM3, GSTA4, GGCT, GPX3, IDH2, GSTT1

3.328363636 0.118323547 5.599127941

hsa04510:Focal adhesion 0.00540645

PIK3CG, COL4A2, VAV3, COL4A1, COL3A1, BIRC3, COL5A2, COL4A6, CCND2, ITGB7, ILK, COL6A3, COL1A2, PDGFRB, LAMC2, PDGFD, COL1A1, THBS2, COL11A1, THBS4, SPP1

1.931886024 0.115172333 6.323111142

hsa00910:Nitrogen metabolism

0.00660909

GLUL, CA9, CA8, CA4, CA2, CPS1 4.823715415 0.122749571 7.678836639

hsa00330:Arginine and proline metabolism

0.006850101

ABP1, GLUL, CKM, ASS1, MAOA, CKMT2, GAMT, CPS1, CKB

3.139965695 0.113674587 7.948353105

hsa00140:Steroid hormone biosynthesis

0.010712635

AKR1C3, AKR1C2, CYP3A5, UGT2B17, AKR1C4, UGT2B10, UGT2B15, UGT2B7

3.215810277 0.156480935 12.17044756

hsa04610:Complement and coagulation cascades

0.011050903

C7, F12, FGG, FGA, C6, SERPINA5, C5, CFH, CFD, PLAU

2.679841897 0.147527842 12.53161361

hsa00040:Pentose and glucuronate interconversions

0.013851199

UGT2B17, UGT2B10, UGT2B15, UGT2B7, DCXR 5.136363636 0.167772099 15.46958327

hsa00591:Linoleic acid metabolism

0.015495549

CYP3A5, AKR1B15, CYP2C18, CYP2C9, AKR1B10, PLA2G1B, PLA2G2A

3.962337662 0.172879525 17.15232225

hsa00260:Glycine, serine and threonine metabolism

0.023499382

MAOA, PHGDH, GAMT, GNMT, CBS, GLDC 3.57888563 0.235377559 24.91296823

hsa00280:Valine, leucine and isoleucine degradation

0.02914714

BCKDHA, DBT, ALDH6A1, BCAT2, HMGCS2, HADH, ACAT1

2.941735537 0.267710798 29.98156893

Supplementary Table 2. The significant KEGG pathways reported by DAVID in GSE13861. The input genes in DAVID were selected with fold-change 2. The significance cutoff was Benjamini false discovery rate (column Benjamini) < 0.3. The column description refers to the DAVID webpage (david.abcc.ncifcrf.gov).

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KEGG identifier:description NES NOM p-val FDR q-valHSA05131:PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC 1.61276 0.006410257 0.1019601HSA00790:FOLATE_BIOSYNTHESIS 1.5625813 0.006122449 0.14507739HSA03030:DNA_POLYMERASE 1.5346949 0.011605416 0.16138485HSA04330:NOTCH_SIGNALING_PATHWAY 1.468798 0.028462999 0.17380403HSA03050:PROTEASOME 1.4508364 0.06930693 0.18814272HSA04110:CELL_CYCLE 1.4723866 0.032128513 0.18969329HSA01430:CELL_COMMUNICATION 1.4837731 0.013861386 0.1963522HSA04320:DORSO_VENTRAL_AXIS_FORMATION 1.424682 0.046025105 0.20109646HSA05130:PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC.. 1.61276 0.006410257 0.2039202HSA03022:BASAL_TRANSCRIPTION_FACTORS 1.4962174 0.014492754 0.20810835HSA04540:GAP_JUNCTION 1.4255977 0.024291499 0.21912435HSA05222:SMALL_CELL_LUNG_CANCER 1.3962696 0.052301254 0.22388233HSA04530:TIGHT_JUNCTION 1.3779125 0.03245436 0.22621876HSA05219:BLADDER_CANCER 1.3859752 0.035785288 0.22802122HSA03010:RIBOSOME 1.397046 0.15670103 0.24111556HSA00240:PYRMIDINE_METABOLISM 1.3551359 0.08582834 0.25662658HSA04742:TASTE_TRANSDUCTION -1.7586877 0.001976285 0.01200752

Supplementary Table 3. The significant KEGG pathways reported by GSEA in GSE13861. The significance was set to FDR q-value < 0.3. The column description refers to GSEA webpage (www.broadinstitute.org/gsea/).

Page 7: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

KEGG identifier Description Entries in the significant subpathways belonging to the pathway

hsa04810 Regulation of actin cytoskeleton FGFR2,HRAS,PIK3CB,SOS2

hsa04370 VEGF signaling pathway KDR,SRC,RAC2,PIK3CB

hsa05214 Glioma HRAS,PIK3CB,SHC3,SOS2,GRB2

hsa04630 Jak-STAT signaling pathway IL9R,CBLC,IL7R,STAT6,PIK3CG,CISH,PIAS4,IL22RA2,PIK3CD,CSF2RB,LEPR,AKT2,STAM,AKT1,JAK2,IL20RB,TYK2,CBL,IL10RA,AKT3,SOCS7,SOCS2,MYC,CREBBP,STAT4,IL13RA2,CCND1,PIK3R2,SOCS3,CBLB,STAT2,PIAS1,SOCS1,IFNAR2,IL2RA,PIM1,CCND3,STAT5B,PIAS3,STAT1,PIK3R3,SOCS5,IFNGR1,JAK3,PIK3CB,EP300,IFNGR2,JAK1,CNTFR,IFNAR1,CSF3R

hsa04330 Notch signaling pathway NUMB,JAG2,PTCRA,RBPJL,NOTCH2

hsa04062 Chemokine signaling pathway CCL22,GSK3A,LYN,XCL1,HCK,NFKBIA,PTK2,CCL21,GNB5,GNG12,AKT1,JAK2,CCL8,CHUK,CXCL6,GRK6,GNG8,GNGT1,CCL26,AKT3,STAT3,PLCB1,ARRB2,VAV3,CXCR4,GRK7,CXCL14,CCL1,CCL2,ITK,RELA,CCL7,PRKCD,CCR9,PAK1,STAT2,CCL5,RAC2,CCL23,GRK5,CXCL11,PRKACG,FOXO3,CSK,CX3CR1,PIK3CB,CXCL12,ADCY6,CCR3,PXN,VAV1,CCL16,PIK3CG,CCL24,NCF1,PIK3CD,CCL17,CCL19,CX3CL1,CXCL2,AKT2,GNAI1,IKBKB,GNAI3,FGR,CCR2,CCL3,CCL18,PTK2B,CCL15,CCR6,GNB1,GRK4,CXCR3,PIK3R2,ADRBK2,PIK3CA,GNB3,CXCL16,CCL4,GNB2,PF4,PIK3R3,JAK3,CCR1,CCR4,CCL13,CXCL5,CRKL,GNAI2,IL8,CCL27,ARRB1

hsa04664 Fc epsilon RI signaling pathway MAP2K3,RAC1,MAPK11,PIK3CB,VAV3

hsa05215 Prostate cancer NFKBIA,PDPK1,PIK3R5,IKBKB,AKT3,PDGFC,CASP9,EGFR

hsa04114 Oocyte meiosis PLCZ1,CAMK2G,ITPR1,CDC25C,CALM2

hsa04010 MAPK signaling pathway CACNA1A,CACNA1D,PLA2G12B,PLA2G4B,CACNA1I,RAF1,CASP3,PAK2,NRAS,CACNA2D4,IL1R2,MAPK3,ELK1,MAP2K2,CACNA1G,CACNB3,MAP3K2,CACNB2,MKNK2,RASGRF1,CACNG2,PLA2G1B,RASGRF2,CACNA1E,CACNG3,MAPT,CACNA1H,CACNA1S,ATF4,CACNG5,CACNA1B,RASGRP3

hsa05100 Bacterial invasion of epithelial cells

ARPC5,GAB1,WASL,ACTB,PIK3R1,PIK3CG,ARPC1A,PIK3CD,CDC42

hsa04510 Focal adhesion FLT4,VAV1,VEGFA,PIK3CG,ITGA3,PDGFC,SOS2,PAK2,PIK3CD,ELK1,PTK2,MAP2K1,EGFR,ITGB4,PAK6,EGF,PIP5K1C,VEGFB,SHC2,VCL,PDGFRA,ACTN3,PIK3R5,FYN,MET,VAV3,PGF,ITGB1,VEGFC,PIK3R2,KDR,MAPK3,RAC1,HRAS,RAC2,HGF,CCND3,PDGFB,PTEN,BIRC3,PDGFRB,PIK3R3,SHC3,FIGF,ERBB2,FLT1,GRB2

hsa04310 Wnt signaling pathway LRP5,VANGL1,VANGL2,DVL3,SFRP4,WNT2B,DKK4,WIF1,WNT9B,CER1,SFRP2,WNT9A,PORCN,FZD8,FZD1,WNT2,CSNK2A2,FZD6,WNT7A,SFRP1,WNT3,WNT10A

hsa04360 Axon guidance SEMA4G,RAC1,PLXNB1,PAK2,SEMA4C

hsa04666 Fc gamma R-mediated phagocytosis

SYK,LYN,FCGR1A,PRKCD,RAC1,PIK3CA,PLCG2,ARPC4,ARPC1B,WASF3,PTPRC,FCGR3A,ARPC2,VAV3,MARCKSL1,MARCKS

Supplementary Table 4. The 15 KEGG pathways containing the significant 126,095 subpathways in GSE15081. The significance of a supathway was set to FDR-q value < 0.05. For the comparison, all the significant subpathways were assigned to their pathways.

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KEGG identifier:description

P-Value Genes Fold Enrichment Bonferroni FDR (%)

hsa05219:Bladder cancer

0.029916482 IL8, MYC, MMP1 10.68277311 0.926618798 27.9292983

Supplementary Table 5. The significant KEGG pathways reported by DAVID in GSE15081. The input genes in DAVID were selected with fold-change 1.25. The significance cutoff was Benjamini false discovery rate (column Benjamini) < 0.3. The column description refers to the DAVID webpage (david.abcc.ncifcrf.gov/).

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KEGG identifier:description

NES NOM p-val FDR q-val

HSA03050:PROTEASOME -1.9035194 0.002040816 0.053505477HSA00710:CARBON_FIXATION -1.714285 0.00203666 0.24290548

Supplementary Table 6. The significant KEGG pathways reported by GSEA in GSE15081. The significance was set to FDR q-value < 0.3. The column description refers to GSEA webpage (www.broadinstitute.org/gsea/).

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CSNK2B FZD2 NLKMMP7 CSNK1A1L FZD3PLCB4 DKK4 CER1CTNNB1 WNT4 PORCNSFRP2 WNT6 FZD4CCND1 FZD5 DVL1MAP3K7 WNT7A AXIN2CCND3 DVL3 DVL2PRKX NFATC4 WNT9BWIF1 MYC WNT2WNT5A FZD6 TCF7L2WNT10A FZD1 PLCB1VANGL1 PSEN1 PRKCGWNT2B FZD8 NFATC1CSNK2A1 VANGL2 FZD10SFRP1 TCF7 PRKCAPPP3CB PPP3CC WNT9ACCND2 PRKACB SFRP4CAMK2B CAMK2D LRP5CSNK2A2 PPARD WNT10BWNT3 CSNK1A1

Supplementary Table 7. The 62 genes belonging to the combined significant subpathways in the discovery stage. 

Page 11: Supplementary Figure 1A HNF4AWNT5AVANGL1PCLB1 Supplementary Figure 1B Supplementary Figure 1. (A) HNF4A TFBSs of the three genes: VANGL1, WNT5A and PLCB1.

Supplementary Table 8. The expression concordance among the four datasets (GSE13861, GSE36968, GSE15081, GSE27342) in terms of the 62 genes of the combined subpathways in the discovery stage. The similarity was measured by Fisher’s exact test.

Dataset GSE36968 GSE15081 GSE27342

Dataset Group Up1 Down1 Total Up2 Down2 Total Up1 Down1 Total

GSE13861

Up1 22 8 30 22 15 37 14 5 19

Down1 6 13 19 10 12 22 5 11 16

Total 28 21 49 32 27 59 19 16 35

P-value 0.007136 0.4182 0.01849

1Up/Down regulated genes in GC cells over normal-appearing cells.2Up/Down regulated genes in GC peritoneal relapse over non-relapse.