<<

Figure S1. Representative report generated by the Ion Torrent system server for each of the KCC71 panel analysis and PCaFusion analysis. (A) Details of the run summary report followed by the alignment summary report for the KCC71 panel analysis sequencing. (B) Details of the run summary report for the PCaFusion panel analysis.

A Figure S1. Continued. Representative report generated by the Ion Torrent system server for each of the KCC71 panel analysis and PCaFusion analysis. (A) Details of the run summary report followed by the alignment summary report for the KCC71 panel analysis sequencing. (B) Details of the run summary report for the PCaFusion panel analysis.

B Figure S2. Comparative analysis of the variant frequency found by the KCC71 panel and calculated from publicly available cBioPortal datasets. For each of the 71 in the KCC71 panel, the frequency of variants was calculated as the variant number found in the examined cases. Datasets marked with different colors and sample numbers of are presented in the upper right. *Significantly high in the present study. Figure S3. Seven subnetworks extracted from each of seven public prostate cancer networks in TCNG (Table SVI). Blue dots represent genes that include initial seed genes (parent nodes), and parent‑child and child‑grandchild genes in the network. Graphical representation of node‑to‑node associations and subnetwork structures that differed among and were unique to each of the seven subnetworks. TCNG, The Cancer Network Galaxy. Figure S4. REVIGO tree map showing the predicted biological processes of prostate cancer in the Japanese. Each rectangle represents a biological function in terms of a (GO) term, with the size adjusted to represent the P‑value of the GO term in the underlying GO term database. Superclusters are differentially colored. Detailed information is also presented in Table SVIII. REVIGO, Reduce + Visualize Gene Ontology. Table SI. List of genes included in the KCC71 and PCsFusion panels.

KCC71 PCaFusion ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ PIK signal AR signal RAS signal Other Fusion Control

AKT1 AR BRAF APC ETV1 ACSL3‑ETV1 MPP5‑FAM71D KLK3 PIK3C3 TNK2 KRAS GSK3B SPOP ARHGEF3‑C8orf38 NDRG1‑ERG SLC45A3 PIK3CA FOXA1 NRAS EGFR MED12 CANT1‑ETV4 RAD50‑PDLIM4 SPINK1 PIK3CG AMACR HRAS FGFR1 C14orf49 CTAGE5‑KHDRBS3 RNF19A‑SNX31 HMBS PIK3R1 ELAC2 RAF1 FAT4 NRIP1 DCAF6‑MPZL1 RP11_EST14‑ETV1 TBP PIK3R3 KDM4B EPHB2(ERK) IDH1 ZNF595 DDX5‑ETV4 SDK1‑AMACR ITGB7 PTEN PXN INPP4B NIPA2 DOT1‑HES6 SERF2‑PDIA3 PTK2B DNA repair PTPN3 EP300 THSD7B ESRP1‑RAF1 SLC45A3‑BRAF LMNA PHLPP1 BRCA1 PTPN11 FREM2 SCN11A FLJ35294‑ETV1 SLC45A3‑ELK4 NBS1 BRCA2 HMCN1 MXI1 FOXP1‑ETV1 SLC45A3‑ETV1 MSH6 HOXB3 NKX3‑1 GABPB2‑BNIPL SLC45A3‑ETV5 ATBF1 KLF6 SPRY1 HERPUD1‑ERG SNURF‑ETV1 Cell cycle SOX9 SPRY2 HERVK‑ETV1 THADA‑MAP4K3 CCNE1 MAP3K2 SPTA1 HERVK17‑ETV1 TMPRSS2‑ERG CHEK2 LRP1B TFG HMGN2PC15ORF21‑ETV1 TMPRSS2‑ETV1 RB1 MSR1 HNRPA2B1‑ETV1 TMPRSS2‑ETV4 TP53 PDZRN3 KLK2‑ETV4 TMPRSS2‑ETV5 CDH1 RNASEL/HPC1 LAMA5‑AATK TSPAN4‑PHRF1 CDK2 LRBA‑NFKB1 USP9Y‑TTTY15 p21 CDKN1B Table SIII. Detailed information on variants found in the KCC71 panel analysis.

COSMIC (v82) Gene ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ symbol a.a. change Transcript Coding Allele frequency (%) Numbers Tumor type FATMM (score) Mutation ID Sample

AKT1 G233A NM_001014431.1 c.698_699 23.5 Not reported ‑ 1 delGCinsCG AR K610E NM_000044.3 c.1828A>G 5.6 1 Prostate N/A COSM5954481 7 ATBF1 T550A NM_006885.3 c.1648A>G 25 Not reported 14 ATBF1 Y1088ter NM_006885.3 c.3264C>G 26.6 Not reported 3 BRAF K601E NM_004333.4 c.1801A>G 60.9 97 , skin Pathogenic COSM478 14 and others (0.98) BRCA1 S1598P NM_007300.3 c.4792T>C 46.4 Not reported 2 BRCA2 T582P NM_000059.3 c.1744A>C 46.6 Not reported 15 BRCA2 I1859fs NM_000059.3 c.5574_5577 71.5 Not reported 13 delAATT BRCA2 R2318ter NM_000059.3 c.6952C>T 56.1 Not reported 6 CDH1 G62V NM_004360.3 c.185G>T 52.8 1 N/A COSM19514 15 CDH1 E880K NM_004360.3 c.2638G>A 46.3 1 Breast Pathogenic COSM6023987 9 (0.99) CDK2 G176A NM_001798.3 c.527G>C 14.8 Not reported 16 ELAC2 S587L NM_001165962.1 c.1760C>T 54 Not reported 12 FAT4 M4369V NM_024582.4 c.746T>G 38.3 Not reported 17 FOXA1 R265‑K267. NM_004496.3 c.793_801del 12.4 R265‑K270, 1 Prostate N/A COSM5547638 16 del CGCTTCAAG HMCN1 A4944V NM_031935.2 c.14831C>T 10 Not reported 10 KDM4B G711S NM_015015.2 c.2131G>A 6.1 Not reported 5 KDM4B R813G NM_015015.2 c.2437A>G 10.3 Not reported 4 LRP1B P4480S NM_018557.2 c.13438C>T 54.2 Not reported 12 LRP1B A4530V NM_018557.2 c.13589C>T 67 Not reported 3 LRP1B V1608I NM_018557.2 c.4822G>A 39.7 Not reported 5 PHLPP1 P394A NM_194449.3 c.1180C>G 18.8 Not reported 16 RAF1 A586T NM_002880.3 c.1756G>A 11.1 Not reported 15 RB1 R621S NM_000321.2 c.1861C>A 31.2 3 (7) Hemat Pathogenic COSM1046 8 logical, pituitary, (0.93) SOX9 A372P NM_000346.3 c.1114G>C 71.3 Not reported 1,5 SPOP F102V NM_001007228.1 c.304T>G 27 7 (18) Prostate Pathogenic COSM4393128 10 (0.99) Table SIII. Continued.

COSMIC (v82) Gene ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ symbol a.a. change Transcript Coding Allele frequency (%) Numbers Tumor type FATMM (score) Mutation ID Sample

SPOP F133L NM_001007228.1 c.399C>G 13.2 35 (80) Prostate Pathogenic COSM95272 11 (0.92) C14orf49 R37H NM_152592.3 c.110G>A 14.2 Not reported 17 THSD7B G402S NM_001080427.1 c.1204G>A 33.9 3(4) n/a N/A COSM3566910 13 TNK2 Q10R NM_001010938.1 c.29A>G 43.8 Not reported 17 TP53 V31I NM_000546.5 c.91G>A 33.3 11 Various Neutral COSM4169628 2 ZNF595 V74A NM_001286053.1 p.Val74Ala 12.5 Not reported 1 ZNF595 V263fs NM_001286053.1 c.788_789insA 17.4 Not reported 8 Table SIV. Mutation percentage in 71 genes in each dataset.

Gene KCC71 TCGA Broad.mt.edu Memorial Sloan Fred Hutchinson symbol (21) (499) (477) Kettering (504) CRC (176)

AKT1 4.8 0.6 0.2 0.0 1.4 AR 0.0 0.6 0.5 3.2 5.7 ATBF1 14.3 0.0 0.0 0.0 0.0 BRAF 4.8 1.6 0.7 1.1 0.0 BRCA1 4.8 0.2 0.0 0.0 0.7 BRCA2 14.3 1.8 0.0 2.2 0.7 C14orf49 4.8 0.0 0.0 0.0 0.0 CDH1 9.5 0.8 0.2 1.1 0.0 ELAC2 4.8 0.0 0.0 0.0 0.0 FAT4 4.8 2.4 0.5 0.0 5.7 FOXA1 4.8 5.6 2.5 0.0 2.8 HMCN1 4.8 0.0 1.1 0.0 0.0 KDM4B 9.5 0.0 0.0 0.0 0.0 LRP1B 14.3 4.8 1.1 0.0 11.4 PHLPP1 4.8 0.0 0.0 0.0 0.0 RAF1 4.8 0.2 0.0 0.0 0.0 RB1 4.8 0.6 0.2 0.0 5.0 SPOP 4.8 11.4 8.5 0.0 7.1 THSD7B 4.8 0.0 1.1 0.0 0.0 TNK2 4.8 0.0 0.0 0.0 0.0 TP53 4.8 12.2 3.6 2.2 40.4 ZNF595 9.5 0.0 0.0 0.0 0.0 Table SV. Fisher's test on the KCC71 panel set and number of variants in each dataset.

TCGA Broad Fred Memorial ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ P‑value P‑value P‑value P‑value Pathway Gene (Fisher's log10) (Fisher's log10) (Fisher's log10) (Fisher's log10

PIK3 AKT1 0.82 1.08 0.69 1.40 AR AMACR 1.39 1.38 0.97 1.40 Other APC 0.00 0.00 0.00 0.00 AR AR 0.00 0.00 0.00 0.00 Repair ATBF1 4.24 4.19 2.97 4.26 RAS signaling BRAF 0.51 0.80 0.44 0.66 Repair BRCA1 1.10 1.38 0.97 1.40 Repair BRCA2a 2.00 4.19 2.97 1.82 Other C14orf49 1.39 1.38 0.97 1.40 Cell cycle CCNE1 0.00 0.00 0.00 0.00 Cell cycle CDH1a 1.67 2.30 1.52 1.55 Cell cycle CDK2 1.39 1.38 0.97 1.40 Cell cycle CDKN1B (p27/Kip) 0.00 0.00 0.00 0.00 Cell cycle CHEK2 0.00 0.00 0.00 0.00 Other EGFR 0.00 0.00 0.00 0.00 AR ELAC2 1.39 1.38 0.97 1.40 Other EP300 0.00 0.00 0.00 0.00 RAS signaling EPHB2 0.00 0.00 0.00 0.00 Other ETV1 0.00 0.00 0.00 0.00 Other FAT4 0.38 0.92 0.54 1.40 Other FGFR1 0.00 0.00 0.00 0.00 AR FOXA1 0.15 0.36 0.11 1.40 Other FREM2 0.00 0.00 0.00 0.00 Other GSK3B 0.00 0.00 0.00 0.00 Other HMCN1 1.39 0.64 0.30 1.40 Other HOXB1 0.00 0.00 0.00 0.00 Other HOXB3 0.00 0.00 0.00 0.00 RAS signaling HRAS 0.00 0.00 0.00 0.00 Other IDH1 0.00 0.00 0.00 0.00 Other INPP4B 0.00 0.00 0.00 0.00 AR KDM4Ba 2.81 2.77 1.96 2.82 Other KRAS 0.00 0.00 0.00 0.00 RAS signaling KLF6 0.00 0.00 0.00 0.00 Other LRP1B 1.05 2.50 1.38 4.26 Other MAP3K2 0.00 0.00 0.00 0.00 Other MED12 0.00 0.00 0.00 0.00 Repair MSH6 0.00 0.00 0.00 0.00 Other MSR1 0.00 0.00 0.00 0.00 Other MXI1 0.00 0.00 0.00 0.00 PIK3 NBS1 0.00 0.00 0.00 0.00 Other NIPA2 0.00 0.00 0.00 0.00 Other NKX3‑1 0.00 0.00 0.00 0.00 RAS signaling NRAS 0.00 0.00 0.00 0.00 Other NRIP1 0.00 0.00 0.00 0.00 Cell cycle p21 0.00 0.00 0.00 0.00 Other PDZRN3 0.00 0.00 0.00 0.00 PIK3 PHLPP1 1.39 1.38 0.97 1.40 PIK3 PIK3C3 0.00 0.00 0.00 0.00 PIK3 PIK3CA 0.00 0.00 0.00 0.00 PIK3 PIK3CG 0.00 0.00 0.00 0.00 PIK3 PIK3R1 0.00 0.00 0.00 0.00 PIK3 PIK3R3 0.00 0.00 0.00 0.00 PIK3 PTEN 0.00 0.00 0.00 0.00 PIK3 PTK2B 0.00 0.00 0.00 0.00 PIK3 PTPN11 0.00 0.00 0.00 0.00 RAS signaling PTPN3 0.00 0.00 0.00 0.00 Table SV. Continued.

TCGA Broad Fred Memorial ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ P‑value P‑value P‑value P‑value Pathway Gene (Fisher's log10) (Fisher's log10) (Fisher's log10) (Fisher's log10

AR PXN 0.00 0.00 0.00 0.00 RAS signaling RAF1 1.10 1.38 0.97 1.40 RAS signaling RAN 0.00 0.00 0.00 0.00 Cell cycle RB1 0.82 1.08 0.69 1.40 Other RNASEL/HPC1 0.00 0.00 0.00 0.00 Other SCN11A 0.00 0.00 0.00 0.00 Other SOX9a 2.05 2.77 1.96 2.82 Other SPOP 0.04 0.07 0.00 1.40 Other SPRY1 0.00 0.00 0.00 0.00 Other SPRY2 0.00 0.00 0.00 0.00 Other SPTA1 0.00 0.00 0.00 0.00 Other TFG 0.00 0.00 0.00 0.00 Other THSD7B 1.39 0.64 0.30 1.40 AR TNK2 1.39 1.38 0.97 1.40 Cell cycle TP53 0.03 0.26 0.06 0.41 Repair ZNF595a 2.81 2.77 1.96 2.82 aP<0.05 was considered to indicate statistically significant differences. Table SVI. GEO ID and information for 7 prostate cancer datasets.

GEO ID Platform Samples Publications

GSE6956 [HG‑U133A_2] Affymetrix Genome 33 of African‑American and 36 of Cancer Res. 2008 Feb 1;68(3):927‑36. doi: 10.1158/0008‑5472. U133A 2.0 Array European‑American patients primary CAN‑07‑2608. prostate tumors GSE8218 [HG‑U133A] Affymetrix 148 of prostate samples, with various Cancer Res. 2011 Apr 1;71(7):2476‑87. doi: 10.1158/0008‑ U133A Array amounts of tumor, stroma, BPH and 5472.CAN‑10‑2585., Cancer Res. 2010 Aug 15;70(16): atrophic gland, were used for this study 6448‑55. doi: 10.1158/0008‑5472.CAN‑10‑0021. Epub 2010 Jul 27. GSE14206 Agilent‑012097 Human 1A Microarray (V2) 59 of primary prostate cancer and PLoS One. 2010 May 10;5(5):e10547. doi: 10.1371/journal. G4110B (Feature Number version) normal 14 of prostate clinical samples pone.0010547. GSE16120 Agilent‑012097 Human 1A Microarray 51 of prostate cancer tissues Peraldo‑Neia et al. BMC Cancer 2011, 11:31 (V2) G4110B (Feature Number version) http://www.biomedcentral.com/1471‑2407/11/31 GSE17951 [HG‑U133_Plus_2] Affymetrix Human 154 of prostate sample with various Jia Z et al., ‘Diagnosis of prostate cancer using Genome U133 Plus 2.0 Array amount of different cell types differentially expressed genes in stroma.’, Cancer Res, 2011 Apr 1;71(7):2476‑87, Wang Y et al., ‘In silico estimates of tissue components in surgical samples based on expression profiling data.’, Cancer Res, 2010 Jul 27;70(16):6448‑55 GSE25136 [HG‑U133A] Affymetrix Human Genome 79 of prostate cancer Prostate. 2009 Jul 1;69(10):1119‑27. doi: 10.1002/pros.20961. U133A Array GSE32269 [HG‑U133A] Affymetrix Human Genome 22 of primary Pca (hormone‑dependent) J Clin Invest. 2013 Mar;123(3):1109‑22. doi: 10.1172/ U133A Array versus 29 of metastatic Pca (CRPC) JCI66666. Epub 2013 Feb 15.

The table shows each GEO ID, platform, sample information, and related literature of seven prostate cancer cases registered in TCNG. Table SVII . Gene list in the core networks.

AADAC AMD1 BAGE4 C1QTNF1 CD5 COMMD4 DDX28 EIF5A FBXL2 GATA2 ABCA3 AMPD1 BAHCC1 C20orf7 CD6 COPA DDX6 EIF6 FBXO22 GCK ABCC1 ANGEL2 BAI1 C22orf29 CD79A CORT DEPDC6 ELF1 FCN3 GCM2 ABCC4 ANGPT1 BAIAP2L2 C5 CDA COX18 DGKA ELF3 FCRL3 GCNT2 ACBD4 ANK3 BBC3 C6orf103 CDH1 CPB1 DGKQ ELL2 FDPS GGA2 ACE ANKLE2 BCAT1 C6orf58 CDH4 CPNE1 DHCR24 EML3 FDXACB1 GGT1 ACLY ANKRD6 BCL2L1 C7orf13 CDH7 CREB3L1 DHCR7 EMX2 FDXR GGT2 ACOT13 ANXA1 BCL2L11 C7orf63 CDK19 CRISPLD1 DHX9 ENC1 FEZ1 GGT3P ACOXL ANXA5 BCL3 C8orf4 CDK5RAP2 CRTAC1 DIAPH1 ENOX1 FGF13 GGTLC1 ACPP AP1S1 BCL7A C8orf41 CDKN1A CRTAP DICER1 ENTPD5 FGFBP3 GGTLC2 ACSL5 AP3S2 BDKRB2 C9orf114 CDO1 CRYBB2P1 DIO3 EPHB3 FHOD3 GGTLC3 ACSM3 AP4E1 BEGAIN C9orf45 CEACAM3 CRYM DIXDC1 EPHB4 FKBP1A GHRHR ADAM3A APLP2 BEND7 CA2 CENPN CSGALNACT1 DKFZP434H168 EPHX2 FKBP4 GIGYF2 ADAT2 APOA2 BEST1 CA4 CEPT1 CSH1 DLG3 EPN3 FKBP5 GLUD2 ADCK4 APP BEX1 CA5BP CETN1 CSNK2A1 DLG4 ERG FKTN GLYR1 ADH1C AQP9 BHLHE41 CAB39L CFB CSNK2A1P DMXL1 ERGIC3 FLJ38668 GNA11 ADNP2 AR BIK CACNB3 CFLAR CST1 DNAJC19 ERLIN1 FLT3 GNAS AGAP1 ARC BIRC5 CACNG4 CHD7 CST3 DOCK11 ESR1 FLT4 GNB5 AGAP2 ARF6 BLZF1 CADM4 CHEK1 CTAG2 DOK2 ESR2 FMOD GNL1 AGFG2 ARFGAP3 BMPR1A CALD1 CHEK2 CTBP2 DPP4 ESRRB FNBP1L GOLGA6L6 AGR2 ARFGEF1 BMPR1B CALML5 CHM CTLA4 DSC2 FNDC4 GOT1L1 AGTR1 ARHGAP32 BNC1 CANX CHPT1 CTNND2 DSG2 EXTL1 FNDC8 GP2 AIM1 ARHGEF3 BNIP3 CAP2 CHRD CTSK DSP EYA2 FOLH1 GPER AIM1L ARL4A BRD4 CARD10 CHST8 CUX2 DUOX2 F11R FOLH1B GPHN AIM2 ARSD BTG1 CARKD CLDN3 CWH43 DUSP21 F12 FOXA1 GPR107 AIMP1 ART4 C11orf21 CASP1 CLDN7 CXorf56 DUSP26 F2RL1 FOXD2 GPR135 AIPL1 ASPHD2 C11orf63 CATSPERG CLEC4C CXXC1 DUSP4 F3 FPR1 GPR176 AK1 ASRGL1 C11orf75 CBFA2T2 CLMN CXXC4 DYNC1H1 FABP3 FRAT2 GPR37L1 AK5 ASTE1 C12orf4 CBR3 CLRN1 CYB561 FABP4 FRMD1 GPR39 AKAP1 ATF7IP C12orf45 CCDC27 CMKLR1 CYLC1 ECE2 FAM115A FTH1 GPR44 AKR1B1 ATP1A1 C12orf47 CCDC85A CNDP2 CYorf15B ECT2 FAM115B FUCA2 GPR56 AKR1C1 ATP1B2 C14orf25 CCDC94 CNNM3 CYP1A1 EDIL3 FAM118A FURIN GPR89B AKR1C2 ATP6V1A C16orf3 CCL16 CNP CYP2A13 EEF1A2 FAM124B FUT5 GPRC5C AKR1C3 ATP6V1G1 C16orf53 CCL2 CNTROB CYP2E1 EEF2 FAM155B FZD5 GRAP2 ALDH18A1 ATP7B C17orf39 CCRL1 COBLL1 CYP51A1 EFHC2 FAM198B G3BP2 GREM2 ALDH1A1 ATP8A2 C17orf95 CD22 COBRA1 DACH1 EFNB2 FAM20A GAB2 GRHL2 ALDH1A3 ATP9A C1orf107 CD247 COIL DARC EGFR FAM38A GABRG2 GRIA1 ALDH4A1 ATRX C1orf113 CD2AP COL11A2 DCHS2 EHF FAM65A GAS1 GRIN2C ALDH6A1 ATXN7 C1orf116 CD302 COL4A3BP DCTD EIF2S3 FANCF GAS2 GRIN3B ALX3 ATXN8OS C1orf123 CD44 COL6A2 DDOST EIF4G1 FAT1 GAS2L1 GRIP1 GRK1 HIST1H2BE HIST4H4 HSFX1 IL12B ITGA3 KIAA1614 KTELC1 LOC157627 LONP2 Table SVII . Continued.

GRK4 HIST1H2BF HLA‑A HSP90B1 IL13RA1 ITGA6 KIAA1654 LARP1 LOC202181 LOXHD1 GRSF1 HIST1H2BG HLA‑DRB4 HSPA4L IL18R1 ITGAV KIAA2022 LARS2 LOC388152 LOXL3 GSPT2 HIST1H2BH HMGA1 HSPD1 IL1R1 ITGB1BP1 KIF1B LCP1 LOC440434 LPAR3 GSR HIST1H2BI HMGCS2 HTR7P1 IL1RAP ITPR1 KIF3B LEKR1 LOC442233 LPCAT3 GTF2I HIST1H2BK HMHA1 HYDIN IL1RAPL1 ITPR3 KIR2DL4 LEPREL2 LOC442421 LPPR3 GTF3C2 HIST1H4A HN1L ICAM1 IL4 JAM2 KIR3DL1 LGR4 LOC643837 LRBA GUCA1A HIST1H4B HNRNPF IDH2 IMPAD1 JKAMP KIR3DL2 LIG1 LOC646934 LRCH4 HAPLN2 HIST1H4C HNRNPH2 IDS INCENP JOSD1 KLF12 LILRA5 LOC647070 LRP1 HCRTR2 HIST1H4D HOMER2 IGFBP5 INPP5B KCNA1 KLHL11 LILRB5 LOC654433 LRRC47 HDGF HIST1H4E HOOK1 IGH@ INSIG1 KCNK1 KLHL23 LIPC LOC727751 LRRC8A HEATR1 HIST1H4F HOPX IGHA1 IQSEC3 KCNMB2 KLK12 LMAN1 LOC727787 LRRC8B HEATR6 HIST1H4H HORMAD1 IGHA2 IRF2 KCNN4 KLK13 LOC100131795 LOC727849 LRRN2 HELQ HIST1H4I HOTAIR IGHG1 IRF6 KCNQ4 KLK2 LOC100133761 LOC728412 LSM12 HES1 HIST1H4J HOXB5 IGHG3 IRS1 KCTD21 KLK3 LOC100134355 LOC728800 LSR HEXA HIST1H4K HOXD3 IGHM IRX4 KDM5B KLRD1 LOC100288105 LOC729353 LYPD6B HINFP HIST1H4L HPD IGHVα IRX5 KHDRBS3 KRT12 LOC100288558 LOC729991‑ LYVE1 MEF2B HIST1H1T HIST2H4A HPN IGHV4‑31 ISOC2 KIAA0284 KRT18 LOC100289641 LOC79999 MACROD2 HIST1H2AC HIST2H4B HPX IHH ISYNA1 KIAA1143 KRT24 LOC153682 LOC80154 MAGEL2 HIST1H2BC HIST3H2A HSD17B11 IKBKB ITFG2 KIAA1324 KRT8 LOC157562 LOC92249 MAGOH2 MALT1 MIP MYO5C NGFRAP1 NPAS2 OPRK1 PCCA PDE4B PHLDB2 PMAIP1 MANSC1 MKRN1 MYRIP NID1 NPAT OR1E1 PCDHA1 PDE8B PHLPP2 POFUT1 MAOA MLF1 N4BP2 NIPA2 NQO1 OR1L4 PCDHA10 PDHA2 PIK3R1OS POLE2 MAP3K14 MLLT3 NAAA NIPAL3 NR2E1 OR5I1 PCDHA11 PDIA5 PIKFYVE POLI MAPK1 MLLT4 NAIF1 NIT2 NRXN1 OR6A2 PCDHA12 PDK3 PITRM1 POLR2J MAPK1IP1L MLPH NAT15 NKAIN1 NTM OR7A17 PCDHA13 PDXK PKD2 POMZP3 MAR3 MMP10 NAV2 NKX2‑8 NTS OR7E91P PCDHA2 PDZD2 PKIA PPFIA1 MARCKSL1 MMP15 NBPF3 NKX3‑1 NUBPL ORAI2 PCDHA3 PDZRN3 PKIG PPFIA3 MARCO MPDZ NCAPD3 NKX6‑1 NUCB2 ORM1 PCDHA4 PEPD PKNOX2 PPFIBP2 MBOAT1 MPI NCBP1 NLRP1 NUDT9 OSBPL3 PCDHA5 PEX3 PKP1 PPIA MBOAT2 MRPS9 NCOA2 NLRP2 NUMA1 OTUB2 PCDHA6 PFAS PKP2 PPL MBP MSRB2 NCSTN NLRX1 NUP62 P2RY1 PCDHA7 PFKFB2 PLA1A PPP1R12A MCCC2 MTA2 NDRG1 NMD3 NYX PA2G4 PCDHA8 PGD PLA2G2A PPP5C MED18 MTMR1 NDRG3 NMNAT2 OAF PA2G4P4 PCDHA9 PGLYRP1 PLA2G2E PPRC1 MED6 MUC6 NDUFA5 NOL10 OAS2 PAIP1 PCDHAC1 PGM3 PLA2G4C PRCC MEGF9 MUS81 NEAT1 NOL4 OAZ3 PAN2 PCDHAC2 PHACTR2 PLA2G7 PRDM1 MEPE MXD1 NEDD4L NOMO1 ODC1 PAOX PCLO PHACTR4 PLEKHO1 PRDM9 MERTK MYCBP NEO1 NOMO2 ODF2 PARK2 PCSK1N PHC3 PLIN2 PRDX6 MFAP5 MYCBP2 NET1 NOMO3 OFD1 PARP8 PCSK6 PHKA2 PLK1 PRIM2 MICAL1 MYO18A NGF NOSTRIN OPA1 PATZ1 PDE3B PHKG2 PLXNB2 PRKAR1B PRKCDBP PTMA RAP2A RGS12 RPL18P11 SCGB3A2 SH3BP4 SLC39A7 SPATA20 STAB1 Table SVII . Continued.

PRKCI PTPLA RARB RGS17 RPL22 SCNN1B SH3YL1 SLC39A9 SPATS2L STEAP1 PRKCZ PTPN13 RARRES2 RGS2 RPL26 SCRN1 SHANK2 SLC3A1 SPDEF STEAP4 PRKD3 PTPN22 RASGRP2 RGS20 RPL29P17 SDC4 SHB SLC43A2 SPG7 STIP1 PRODH PTPRE RBM12 RGS4 RPL30 SDF4 SHC2 SLC5A1 SPINT1 SULT1A2 PRPF4 PTPRJ RBM18 RHBDF1 RPL38 SDHA SIDT1 SLC6A8 SPOCK1 SUMO2 PRR14 PTPRZ1 RBM3 RHBDF2 RPRD2 SEL1L3 SIRPA SLC7A11 SPON2 SYCE1L PRRG4 PTTG2 RBM43 RHD RPS6KA3 SELL SLC12A2 SLC7A8 SPOP SYNGR1 PRSS1 PUS7L RBM46 RIMS3 RRAS SEMA4C SLC12A4 SLC9A2 SPP2 SYNJ2 PRSS54 RAB11A RBM47 RIN2 RRP12 SEMG2 SLC17A2 SLCO2A1 SPTBN4 TACSTD2 PRSS8 RAB11B RBM5 RIPK4 RTN1 SEP6 SLC26A2 SMARCC1 SQRDL TAPBP PRUNE2 RAB11FIP1 RCAN3 RNASE1 RUFY2 SERGEF SLC27A2 SNAP91 SRGN TBC1D16 PSAT1 RAB27B RDH11 RND2 RYR2 SERINC2 SLC2A1 SNAPC3 SRP68 TBC1D19 PSD3 RAB2A RERE RNF11P2 S100A11 SERPINC1 SLC2A5 SNORA70 SRPR TBC1D5 PSEN1 RAB3GAP2 RETN RNF6 S100A13 SERPIND1 SLC30A4 SOAT1 SRRM2 TBC1D8 PSEN2 RAB7A RFNG RNFT1 SAMD3 SETBP1 SLC35A2 SORBS2 SRSF10 TBC1D9 PSG7 RAD21 RGPD5 ROD1 SBNO1 SETD8 SLC35E1 SOX17 SSB TBCB PSIP1 RALB RGPD6 RPL10 SCAND2 SF3B3 SLC36A1 SOX30 ST3GAL6 TCEAL4 PSME3 RALGDS RGPD8 RPL11 SCARB2 SGCD SLC38A4 SOX9 ST6GAL1 TCF3 PSPN RANBP3L RGR RPL14 SCD SGSM3 SLC39A6 SPAG11B ST6GALNAC4 TCP10 TEAD3 TMBIM6 TNXB TECTB TMC5 TOP1 TEKT4 TMEM138 TOX3 TERF1 TMEM14B TP53 TESK2 TMEM151B TP53TG5 TFAP2A TMEM176A TPCN2 TFAP2C TMEM176B TPK1 TGM2 TMEM185A TPP1 TGM3 TMEM209 TRAM1 THAP11 TMEM214 TRAPPC10 THBS3 TMEM30B TRBV5‑4 THRB TMEM5 TRIM2 THUMPD1 TMEM52 TRIM27 TIAF1 TMPRSS11A TRIM36 TIAM2 TMPRSS2 TRIM38 TIMM22 TNFAIP1 TRIM48 TJP1 TNFRSF10B TRO TLN2 TNFRSF21 TRPM8 TM7SF2 TNK1 TRPV4 TM9SF4 TNK2 Table SVIII. Evaluation of the genes appearing in the final core network from the aspect of the directed edge numbers and the article numbers related to PCa or simply cancer.

PubMed searcha ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ Gene symbol Seed/common Edge number Symbol x PCa Symbol x cancer

CDH1 Common 69 136 2,765 FOXA1 Common 64 149 603 ZNF350 ‑ 47 0 41 TNX2 Common 42 14 66 SOX9 Common 40 51 72 HOMER2 ‑ 33 0 7 STEAP1 ‑ 32 49 55 CMKLR1 ‑ 28 1 34 PDZRN3 ‑ 25 0 4 ACLY ‑ 25 12 96 PHLDB2 ‑ 24 0 6 ZNF862 ‑ 22 0 1 CANX ‑ 22 3 9 AIM1 ‑ 21 5 33 TP53 Common 20 440 15,021 AR Seed 2 5,998 21,999 SPOP Seed 1 94 162 aArticle numbers obtained through PubMed search (US National Library of Medicine, National Institutes of Health) by ‘gene symbol AND prostate cancer’ and ‘gene symbol AND cancer’. Gene symbols of the top 15 genes and the numbers of edges oriented to each gene are listed in the leftmost column together with all initial seed genes appearing in the final network map. Common, extended common genes; seed, initial seed genes; edge number, numbers of edges oriented to the gene.