Identification of Four Novel Prognosis Biomarkers and Potential Therapeutic Drugs for Human Colorectal Cancer by Bioinformatics Analysis

Available online at www.jbr-pub.org.cn

Open Access at PubMed Central

The Journal of Biomedical Research, 2020 1(0): 1–9

Supplementary Data

Identification of four novel prognosis biomarkers and potential therapeutic drugs for human colorectal cancer by bioinformatics analysis

Zhen Sun1,2, Chen Liu1, Steven Y. Cheng1,3,✉

1Department of Medical Genetics, 2Department of Pathology and Pathophysiology, 3Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Supplementary Table 1 The overlap DEGs from the four GEO datasets analysed by GEO2R Regulation DEGs CLDN1, ENC1, FABP6, ASCL2, FOXQ1, SLC6A6, AXIN2, MRE11A, PPM1H,GART, MYC, SOX4, SYNCRIP, VSNL1, HOMER1, MET, PPAT, CCNB1IP1, TGDS, TRIB3, MACC1, NFE2L3, ATP11A, PLEKHA8, HEATR1, TXLNG, CDH3, XPOT, DPEP1, ZC3HAV1L, CBX3, NUDCD1, DUS4L, TGS1, NEBL, C2, PROCR, RNF43, CKAP2, TOP1MT, RAD54B, SIM2, SLC7A5, HSPH1, RIPK2, LGR5, NUFIP1, NOLC1, SLC39A10, C1orf109, POLR1D, CCT2, CAD, IFITM1, CD44, TMPRSS3, EPHX4, EXOSC5, LRP11, LDLRAD3, NOB1, KRT23, CCDC113, CBX2, NIT2, UTP20, IMMP2L, RPF2, THNSL1, ETV4, ZC3H8, LMBR1, CSE1L, DGAT2, ASPM, CD46, BZW2, SLC22A3, C12orf29, POLR1C, GALNT6, ARMC10, DNAJC2, WDR3, MEST, CBFB, SHROOM4, ZNRF3, HS2ST1, IPO5, NFXL1, BRIX1, PPIL1, PUS7, CDK4, LYAR, PMAIP1, PCID2, AZGP1, KIAA1549, PFDN4, GTF2IRD1, FAM92A1, DARS, PLAU, GTF2F2, NKRF, GPSM2, TMEM123, E2F6, SOX9, UTP14A, WDR12, TEAD4, RPGRIP1L, NOP2, ZNF239, OSBPL3, HAUS6, PRMT3, RNF183, ARNTL2, TCFL5, DCAF13, TMEM97, CCT6A, ZNF280C, CTPS2, UGGT2, EBPL, GTPBP4, INHBA, TEX10, DUSP14, GTF3A, KLF7, MTFR1, SNTB1, CTTNBP2, DDX31, DCUN1D5, CBX4, TGFBI, C10orf2, PROX1, CPNE1, GPATCH2, RAN, LRRC8E, SCD, EIF2S3, PAICS, WDR43, RCL1, SP5, KIF20A, PABPC1L, SCML1, FXYD5, RFC3, PDCD2L, SRPX2, ABCE1, KIF18A, CCDC86, CDCA7, SLCO4A1, LTV1, STC2, XPO4, OGFOD1, PNPT1, ATAD2, DSCC1, SORD, ARID3A, RPP40, MMP7, UBE2C, PAFAH1B3, ECT2, RBM28, Upregulated (n=374) TESC, SHMT2, GNG4, MRPS17, PLCB4, DDX10, AHCY, FARP1, PNO1, SKA3, BYSL, CENPN, POLR1B, PAK1IP1, PODXL, NPM1, RANBP1, E2F5, TACSTD2, FIGNL1, POLA1, GPR180, MPP6, MRTO4, CKS1B, CENPH, NUP35, DACH1, BMP4, CTHRC1, WDR74, PSMG4, SLC6A20, GEMIN5, TRAP1, IFITM3, CFB, NUF2, KLK10, DDX21, URB2, TSPAN5, BID, MCM4, SLC25A32, HSPD1, LGR6, LAPTM4B, EGFL6, MMP1, ESM1, RNASEH2A, DIO2, EEF1E1, FGGY, MCM2, CDC25B, GGH, ELOVL5, XKRX, TAF1A, HELLS, UBE2T, SPC25, CADPS, NCAPD3, ACSL6, PHF19, ERCC6L, FANCI, MSH2, NANP, CENPF, GRHL1, SLC35D3, AURKA, TPX2, CYP4X1, CHI3L1, RUVBL1, SLC12A2, SLC5A6, TOP2A, NCAPG2, DBF4, WDR77, CKS2, COL11A1, CDKN3, MMP3, LRP8, MSX2, TSR1, ANLN, NME1, CEP72, PSAT1, ASB9, CHEK1, C11orf95, TRIP13, CDK1, EIF3B, TBX3, E2F7, CXCL3, TTK, GPR143, RPL37A, NKD1, CLDN2, PRKDC, CKMT2, HOXB8, PMEPA1, TP53RK, DTL, FERMT1, LEF1, HMMR, MAD2L1, SLCO1B3, FEN1, KLK6, TCN1, CXCL1, REG3A, TAF1D, KIF2C, DLGAP5, KLHL7, APCDD1, CDC6, HES6, COL1A1, BUB1, MMP12, COL1A2, KIF4A, STMN3, NEK2, CXCL5, COL12A1, EPHB1, PTTG1, EDNRA, LY6E, SLC7A1, CXCL11, GINS1, ZIC2, GZMB, NCAPG, CDCA3, CDCA5, PTP4A3, PCSK9, EZH2, PLA2G16, KRT6B, MKI67, C2CD4A, FAM83D, PLCB1, WNT5A, NHS, CEL, CEP55, EIF5A2, COL4A1, GRB10, CXCL2, BUB1B, PHLDA1, ADAM12, CCNB1, AGT, BMP7, KIF14, NMU, ITGA2, ZNF367, PRC1, HS6ST2, CFI, GDF15, COL10A1, CCNA2, IGF2BP3, MCM10, KIF23, RRM2

✉Corresponding author: Steven Y. Cheng, Department of Medical August 2020, Epub 22 October 2020 Genetics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and CLC number: R735.3, Document code: A Treatment, Collaborative Innovation Center for Cancer The authors reported no conflict of interests. Personalized Medicine, Nanjing Medical University, 101 Longmian This is an open access article under the Creative Commons Attribu- Avenue, Nanjing, Jiangsu 211166, China. Tel/Fax: +86-25- tion (CC BY 4.0) license, which permits others to distribute, remix, 86869463, E-mail: [email protected]. adapt and build upon this work, for commercial use, provided the Received 13 February 2020, Revised 12 August 2020, Accepted 25 original work is properly cited.

Supplementary Table 1 The overlap DEGs from the four GEO datasets analysed by GEO2R (continued) Regulation DEGs SCARA5, CPM, MMP28, DENND2A, ABCA8, CHGA, LPAR1, C10orf54, ST6GALNAC6, SEMA6A, UGP2, ABI3BP, GCNT2, IL6R, ADH1B, TP53,INP2, EPB41L3, HIGD1A, NEDD4L, SYTL4, SMPD1, SCGN, SMPD3, KIAA0513, KLF4, GLTP, ZZEF1, ITM2A, GSN, TSPAN3, CA7, FAM107B, GCG, THRB, SST, KLF9, CD1D, CPNE8, GNA11, BCAR3, PYY, FRMD3, CXCL12, ATP2A3, CLU, NR3C2, EFNA5, SCIN, THBS1, ETFDH, RELL1, C1orf21, UGDH, PDK4, ACADVL, BEST4, TIAM1, TMEM100, CHST5, SPPL2A, KIF13B, SGK1, ZNF575, FAM107A, LIFR, CNTN3, TMCC3, PRDX6, ANO5, MXD1, OLFM1,KIAA1211, SCNN1B, C2orf88, FRMD4B, BEST2, ENDOD1, MT1M, PLCE1, CHRDL1, ITPKA, RHOU, FAM46A, ENTPD5, STYK1, DNASE1L3, SOCS6, ACADS, HOXD1, CAMK2D, LDHD, VLDLR, EPB41L4A, SLC22A18AS, SLC25A23, SLC4A4, ITM2C, MT1E, SCG2, GHR, SLC25A20, PTP4A1, PLCL2, SCNN1G, GRAMD3, SLC25A34, PARM1, TSPAN7, RHBDL2, PINK1, PTPN21, PDE9A, PTPRH, GUCA2B, FBXO32, DISP2, KCTD9, LRMP, GUCA2A, CDHR5, CACNB2, HRCT1, EDIL3, MT1F, FHL1, CA12, SLCO2A1, CAPN5, KAT2B, EIF4E3, MT1X, INSL5, CLDN23, ALPI, GDPD3, VSIG2, TMEM72, PLCD1, RAB27A, CHP2, SLC2A13, ADCY9, NR5A2, SRPX, MT1H, PRKAR2B, MGLL, C2orf72, TMEM220, RNASEL, LGALS2, CLDN5, PDE4D, ZBTB7C, PADI2, TP53I3, SFRP1, HEPACAM2, ARRDC4, CAPN13, GPD1L, SPON1, IL1R2, SSPN, METTL7A, BMP2, SCGB2A1, DGKA, MT2A, OGN, NAP1L2, B3GALT5, ZG16, SEMA6D, PTGDS, RBM24, C11orf86, CCDC68, GSTA1, SLC13A2, FGL2, C7, LAMA1, ABCG2, VIP, PHGR1, PKIB, DCLK1, RIOK3, SPINK5, MT1G, BTNL3, BCAS1, MUC12, TRANK1, PPP2R3A, PPP1R12B, FGFBP1, PRKACB, SLC22A23, ARL14, SULT1A2, PAG1, TMPRSS2, GREM2, RUNDC3B, CCL28, TPSAB1, PIGR, NR3C1, DHRS11, PROM2, CPT2, VILL, CLMN, JAM2, MAOA, SNX24, AHCYL2, C1orf115, SMPDL3A, VIPR1, SIDT1, SQRDL, CILP, PTGER4, CDA, CWH43, GNAI1, RNF125, CMBL, BEX1, BTNL8, TEX11, CDHR2, TCF21, RCAN2, TRPM6, ACVRL1, FGD4, PDZD3, SRI, ZC3H12C, Downregulated (n=491) DUSP1, SAMD9, SLC30A10, CLIC5, ANK2, RSPO3, GALNT12, MALL, HRASLS2, C16orf62, TMEM171, HPGD, DSC2, SIPA1L2, CLCA4, SYNPO2, B3GNT7, SLC44A4, VWA5A, NKX2-3, MTUS1, SYNPO, MGAT4A, MIER3, PGM1, FNBP1, FAS, TFCP2L1, PLSCR4, ETHE1, CAPN9, HSD17B2, UGT2A3, FLVCR2, RGS13, CLDN8, MYH11, SLC26A3, B3GNT6, HSD11B2, POU2AF1, CDKN2B, NEDD9, C2orf40, CKB, FUCA1, ADH1C, TMEM56, CCL19, MAMDC2, NPY1R, CA1, KIF16B, SGK2, RARRES1, PRKCB, CA2, HHLA2, CHGB, MFAP4, CDC14A, DHRS9, STMN2, SLC22A5, WDR78, HPSE, MYLK, ZBTB16, CITED2, KRT24, CES2, SLC46A3, FMO5, GGT6, LIPH, HDAC9, CA4, FAM46C, KCTD12, SLC41A2, CAPN2, PTGS1, AKR1C1, MTM1, SSTR1, EDN3, SSBP2, USP2, AKR1B10, DPT, PHLPP2, MEIS1, GLIPR2, LRRC19, SULT1A1, LIMA1, EFEMP1, CD36, SLC9A2, FGFR2, NAAA, GBA3, ACACB, PRIMA1, C4orf19, SULT1B1, ACOX1, ISG20, FAM134B, CFD, CYBRD1, SI, MUC2, PIGZ, MS4A1, ST3GAL4, FBLN1, MUC4, BCL2, FCGBP, FXYD3, PAPSS2, CCL5, CLCA1, SLC36A1, CASP7, KCNMA1, BCHE, SLC16A9, AKAP7, MS4A12, IQGAP2, TNFSF10, CD177, CR2, LRRC66, OSBPL1A, TBC1D9, C3orf70, CEACAM1, APPL2, IL11RA, CNR1, EPB41L4B, CEACAM7, TST, MFAP5, EPHA4, SELENBP1, PPARGC1A, SLC17A4, SECTM1, FAM129A, PID1, LXN, MOGAT2, SYNC, CGN,PCK1, GLDN, HGD, HMGCS2, CNTN4, NTRK2, PLAC8, ITLN1, BEX4, GNE, XDH, SDPR, RERGL, TSPAN1, TUBAL3, MYO1A, ABHD3, ATP8B1, GPX3, PEG3, SYTL2, RETSAT, FABP4, PTGDR, RBM47, PRPH, ZSCAN18, MYOCD, ACTG2, SLC28A2, GCNT3, SYNM, STAP2, GAP43, CLIC6, WFDC2, CNN1, MUC5B, NDN, LMOD1, HSPA2, PRELP, KRT20, ANGPTL1, ENPP3, ANPEP, PTGIS, CASP5, SPARCL1, NAT1, PLP1, IL18, AGR3, CASQ2, MAOB, ISX, PLN, TRIM36, AQP8, C10orf99, DES, CCDC80, FABP1, PDE5A, IGFBP6, AMN, CDH19, TMEM30B, SEPP1, DEFB1, ATP1A2, GPM6A, ALDH1A1, SIAE, NAT2, FAM3D, HK2, GPA33, MCOLN2, PTPRR, PPP1R14A, SLC26A2, SFRP2, PCOLCE2, ST6GALNAC1, ABCB1, PGM5, TMEM37, AGTR1, PRKAA2

Novel prognosis biomarkers and drugs for colorectal cancer 3

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID Category Term P-value Genes CXCL1, CKS1B, TSPAN1, CDC14A, POLA1, PRKDC, MCM10, ISG20, CITED2, FAM83D, EDNRA, KIF2C, REG3A, CSE1L, BCL2, TGFBI, GO:0008283~cell GOTERM_BP_DIRECT 3.23e-06 ENTPD5, BUB1, WDR12, AXIN2, MYC, CDK1, MKI67, BYSL, DLGAP5, proliferation MET, PAK1IP1, TPX2, CENPF, ITGA2, DACH1, MXD1, APPL2, GCG, OGFOD1, PLCE1, TACSTD2, CKS2, BUB1B, PYY CKS1B, HAUS6, CDC14A, GNAI1, NEK2, NEDD9, AURKA, NR3C1, PTTG1, FAM83D, SPC25, KIF2C, CDCA7, NCAPG2, NCAPG, BUB1, SKA3, CDCA5, GO:0051301~cell GOTERM_BP_DIRECT 2.76e-06 CCNA2, HELLS, CDCA3, ERCC6L, KIF14, CDK1, CDC6, RAN, NUF2, TPX2, division CENPF, HEPACAM2, UBE2C, CDK4, NCAPD3, CDC25B, CCNB1, MAD2L1, CKS2, BUB1B, RUVBL1 CXCL1, RARRES1, ACVRL1, IFITM1, NDN, E2F7, IGFBP6, SOX4, ZBTB16, GO:0008285~ MSX2, AZGP1, CDKN2B, MYOCD, BCHE, NPM1, AXIN2, FGFBP1, DPT, GOTERM_BP_DIRECT negative regulation of 4.62e-05 BMP4, CDC6, GTPBP4, BMP2, TESC, KAT2B, CLMN, CDKN3, PROX1, cell proliferation INHBA, SFRP1, SFRP2, SSTR1, NME1, EEF1E1, SCIN, UTP20, BMP7, SST, KLF4, FABP6 FGFR2, VIP, EDN3, GCNT2, PRC1, CXCL5, TTK, SOX4, ESM1, SOX9, GO:0008284~positive VIPR1, MYOCD, TIAM1, BCL2, NPM1, WDR77, THBS1, MYC, FGFBP1, GOTERM_BP_DIRECT regulation of cell 0.006789 KIF14, SHMT2, TBX3, LIFR, CHP2, LEF1, IL6R, CDK4, PROX1, PLAC8, proliferation CDC25B, NOP2, SFRP1, SFRP2, NTRK2, FABP1, EIF5A2 GO:0045893~positive WNT5A, CKS1B, ACVRL1, SOX4, ZBTB16, SOX9, ZIC2, CITED2, MYOCD, regulation of AGT, NPM1, ARNTL2, PLCB1, DNAJC2, CCNA2, MYC, BMP4, KLF7, BMP2, GOTERM_BP_DIRECT 0.027221 transcription, DNA- TESC, TBX3, RAN, PCID2, LEF1, ATAD2, PPARGC1A, PROX1, INHBA, templated SFRP1, CKS2, COL1A1, NR5A2, BMP7, NFE2L3, KLF4, TP53INP2 SRI, MMP7, ANPEP, MMP28, MMP3, MMP1, CASP5, CASP7, CD46, KLK10, GO:0006508~ FGL2, C2, CFI, CFD, DPEP1, TMPRSS2, CAPN5, CLCA1, CLCA4, CFB, GOTERM_BP_DIRECT 0.04333 proteolysis CAPN9, GGH, CAPN2, MMP12, TMPRSS3, GGT6, SFRP1, CAPN13, CPNE1, LRP8, ADAM12, TPSAB1, WFDC2, PLAU HAUS6, NEK2, NEDD9, ANLN, AURKA, NR3C1, CEP55, PTTG1, FAM83D, GO:0007067~mitotic SPC25, KIF2C, NCAPG2, BUB1, SKA3, CCNA2, CDCA5, HELLS, ASPM, GOTERM_BP_DIRECT 1.23e-06 nuclear division CDCA3, ERCC6L, CDK1, CENPN, CDC6, RAN, TPX2, NUF2, CENPF, HEPACAM2, CDC25B, NOLC1, BUB1B, RUVBL1 WNT5A, FIGNL1, CBX4, PRKDC, AURKA, SOX9, CITED2, MSX2, CD44, GO:0043066~negative BCL2, NPM1, FAS, PRKAA2, THBS1, MYC, DPEP1, HIGD1A, BMP4, KIF14, GOTERM_BP_DIRECT regulation of apoptotic 0.034931 CDK1, TBX3, PCID2, LEF1, PLAC8, GCG, MAD2L1, SFRP1, DUSP1, process RIPK2, FABP1, HSPD1, TEX11 GO:0043065~positive BID, CLU, PRKDC, SOX4, LPAR1, PMAIP1, ZBTB16, TIAM1, CNR1, FAS, GOTERM_BP_DIRECT regulation of apoptotic 0.002995 TOP2A, FGD4, BMP4, KCNMA1, BMP2, CDK4, ECT2, TNFSF10, DUSP1, process SFRP1, SFRP2, EEF1E1, SCIN, SMPD1, RIPK2, HSPD1, BMP7 SORD, CDH3, BCHE, BCL2, THBS1, MYC, CDK1, MAOB, GGH, ITGA2, GO:0042493~response GOTERM_BP_DIRECT 0.003578 CENPF, ABCB1, ACACB, CDK4, PPARGC1A, ABCG2, CCNB1, INHBA, to drug SFRP1, SFRP2, SMPD1, HSD11B2, LRP8, COL1A1, HSPD1, SST, BCAR3 CCDC86, RNASEL, TSR1, BYSL, PNO1, EXOSC5, NOB1, HEATR1, MRTO4, GO:0006364~rRNA GOTERM_BP_DIRECT 2.87e-04 ISG20, RCL1, DCAF13, NOLC1, RIOK3, WDR3, WDR12, DDX21, RPL37A, processing UTP20, UTP14A, WDR43, LTV1, RPP40, TEX10 BID, SGK1, SGK2, CXCL3, EZH2, PTGS1, CXCL2, CHEK1, CXCL11, SOX9, GO:0042127~regulation GOTERM_BP_DIRECT 6.48e-04 LGR5, AGTR1, STYK1, CDCA7, TCFL5, AGT, PLCD1, FAS, NR5A2, PLAU, of cell proliferation NKX2-3 GO:0030198~ COL4A1, EGFL6, CCDC80, ITGA2, SOX9, SPINK5, ABI3BP, LAMA1, GOTERM_BP_DIRECT extracellular matrix 0.006887 FBLN1, CD44, HPSE, TGFBI, COL1A2, COL1A1, JAM2, THBS1, MFAP5, organization COL11A1, COL10A1 GO:0006260~DNA CDC6, CDK1, DTL, DBF4, POLA1, CHEK1, TOP1MT, MCM2, MCM10, GOTERM_BP_DIRECT 0.003452 replication RNASEH2A, MCM4, C10ORF2, RFC3, RRM2, DNAJC2, FEN1, DSCC1 KCNMA1, BMP2, ACVRL1, AHCY, ITGA2, CAPN2, CXCL12, PRKCB, GO:0001666~response GOTERM_BP_DIRECT 0.00931 CITED2, ASCL2, EDNRA, MYOCD, CAMK2D, HSD11B2, HSPD1, THBS1, to hypoxia PLAU GO:0000082~G1/S CDC6, CDK1, DBF4, POLA1, MCM2, CDKN3, CDK4, MCM10, MCM4, GOTERM_BP_DIRECT transition of mitotic 1.11e-04 RHOU, PPAT, INHBA, RRM2, CAMK2D, RANBP1, CDCA5 cell cycle GO:0000086~G2/M CDK1, CEP72, HAUS6, NEK2, PPP1R12B, TPX2, AURKA, CHEK1, ABCB1, GOTERM_BP_DIRECT transition of mitotic 0.002594 CDC25B, HMMR, CCNB1, PRKAR2B, CDKN2B, PLCB1, PHLDA1 cell cycle GO:0006629~lipid ACOX1, NAAA, CLU, PTGS1, ABHD3, GDPD3, PLCL2, CEL, CD36, PTGDS, GOTERM_BP_DIRECT 0.009175 metabolic process CPNE1, PAFAH1B3, LIPH, MGLL, LRP8, FABP6 4 Sun Z et al. J Biomed Res, 2020, 1(0)

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term P-value Genes GO:0010629~negative XDH, ACVRL1, STC2, PINK1, ACACB, CITED2, CCNB1, SFRP1, SFRP2, GOTERM_BP_DIRECT regulation of gene 0.006558 NME1, AGT, CD46, CPNE1, KLF4, OLFM1 expression GO:0030855~ epithelial GSTA1, FGFR2, CDK1, COL4A1, CDHR2, DHRS9, SPINK5, TST, ACADVL, GOTERM_BP_DIRECT 2.64e-05 cell differentiation TCF21, SULT1B1, BMP7, NR5A2, AKR1C1 CTHRC1, PTGS1, PTPN21, CCT2, PTTG1, LPAR1, ISG20, CITED2, ACTG2, CDCA7, CD44, WDR77, FAS, CDCA5, CCNA2, KIF13B, GTPBP4, RAN, PTPRH, BYSL, PTPRR, EIF2S3, PROX1, FARP1, GLTP, OGFOD1, GRB10, NME1, SSTR1, PGM1, IL1R2, KIF4A, AHCY, NEK2, GNAI1, TFCP2L1, KRT20, IGF2BP3, GPR143, KRT24, SKA3, ARNTL2, MKI67, KLF9, CHI3L1, GART, EPHA4, CEL, SEMA6D, NOLC1, SRPX2, SYTL4, RAD54B, SYTL2, UTP20, KLF4, LIMA1, NAAA, LXN, EZH2, LRRC19, MMP28, SPINK5, MTFR1, CKB, HSPH1, ST6GALNAC6, FANCI, LMOD1, FAM129A, TOP2A, CDC6, ABCE1, CLMN, EXOSC5, GZMB, CCT6A, POLR1B, EPB41L3, RRM2, CLIC5, CLIC6, PFDN4, RUVBL1, LTV1, BID, NKD1, SHROOM4, FHL1, FGGY, EPB41L4A, POLA1, EPB41L4B, PLCL2, FMO5, NCAPG, BCL2, AGT, BUB1, MT1E, PCSK9, PRKAA2, MT1H, MT1G, MT1F, BCAS1, SHMT2, RBM24, MT1M, CAPN5, DLGAP5, CAPN9, ATP1A2, CDKN3, CAPN2, APPL2, MT1X, CD1D, PCK1, CCNB1, PTP4A3, DUSP1, PTP4A1, EEF1E1, MT2A, SAMD9, TUBAL3, PSAT1, NR5A2, PAICS, HPGD, TEX10, TSPAN1, PRC1, NIT2, GNA11, XPO4, GO:0005737~ TTK, IQGAP2, MCM10, SLC7A5, ZIC2, KLHL7, PRKAR2B, REG3A, GOTERM_CC_DIRECT 0.001942 cytoplasm SLC25A20, NUDCD1, CDKN2B, TGS1, DNAJC2, ASPM, PID1, DARS, STMN3, STMN2, DTL, ENC1, CHP2, SOCS6, PKIB, RNASEH2A, METTL7A, GRHL1, MRTO4, ASCL2, PLCE1, GTF2IRD1, RIPK2, LRRC66, NFE2L3, SRI, FGFR2, EIF4E3, GNE, PNPT1, CLU, BEX1, SOX4, NEDD9, BEX4, NHS, CCL5, EIF3B, CSE1L, OSBPL1A, NPM1, AXIN2, FGD4, ERCC6L, CKAP2, GINS1, XPOT, TESC, MYO1A, HRASLS2, PODXL, ARID3A, RPGRIP1L, KCTD9, PLEKHA8, CPNE1, FABP4, FABP1, FBXO32, THNSL1, HSPD1, HDAC9, MYLK, FABP6, LRRC8E, E2F5, CDC14A, FIGNL1, PINK1, PRMT3, FRMD3, BZW2, FAM83D, DCAF13, GSN, CASP7, SDPR, SNTB1, RANBP1, PLCB1, PPP1R14A, CDK1, SGK1, PARM1, SSBP2, LEF1, PADI2, MCM2, UBE2C, ECT2, PRKCB, ACADVL, PRDX6, PPM1H, CAPN13, IPO5, SCIN, FRMD4B, BUB1B, KIAA0513, CA2, CA1, PDCD2L, CASQ2, GAP43, UBE2T, UGP2, HAUS6, PHLPP2, ETHE1, PPP1R12B, NR3C1, CDH3, MACC1, ALDH1A1, MTM1, PAFAH1B3, CAMK2D, GPSM2, PLCD1, NEDD4L, GEMIN5, KLK6, KIF18A, CENPF, DACH1, RCAN2, FUCA1, CDC25B, RGS13, SCGN, CCDC113, GDF15 SLC36A1, GLDN, AQP8, SLC9A2, LPAR1, ZNRF3, AGTR1, MALL, CD44, CD46, FAS, GNG4, NUP35, CDCA5, CLCA1, CLCA4, PTPRR, LIFR, CDHR5, GRB10, CD36, SSTR1, EFNA5, SLC30A10, SLC2A13, IL1R2, GNAI1, CACNB2, GPR143, EPHB1, GPD1L, PROCR, SLC28A2, OSBPL3, KLF9, CFB, ATP11A, ABCG2, EPHA4, FNBP1, SFRP1, SEMA6D, SYTL4, SYTL2, PLAU, LIMA1, ACVRL1, SLC26A2, MTFR1, EDNRA, ST6GALNAC6, CEACAM7, SLC22A3, SLC22A5, TMEM100, FAM129A, CEACAM1, DPEP1, GHR, KCNMA1, C10ORF54, IL6R, ARRDC4, SLC26A3, EPB41L3, STYK1, CLIC6, PTGDR, CYBRD1, ADAM12, NKD1, ALPI, SLC39A10, FHL1, ABHD3, XKRX, ZBTB16, C2ORF88, DISP2, ITM2C, HMMR, ITM2A, DGKA, GPM6A, CD177, PCSK9, FEN1, ACSL6, TMPRSS2, PAK1IP1, NAT2, SI, ATP1A2, NPY1R, CAPN2, CLDN23, CD1D, ADCY9, PLSCR4, PTP4A3, SLC16A9, CDH19, LRP8, VLDLR, GO:0005886~plasma GOTERM_CC_DIRECT 0.023509 TSPAN1, PRC1, SLC44A4, SLC6A20, GNA11, TSPAN5, VIPR1, SLC7A5, membrane RELL1, KLHL7, PRKAR2B, AZGP1, ANK2, TIAM1, TGFBI, PRKACB, MCOLN2, SLC4A4, PAG1, MTUS1, FLVCR2, SLCO4A1, CA12, STAP2, CHP2, IL11RA, PLCE1, LRP11, C2CD4A, AKAP7, WNT5A, ABCA8, FGFR2, FXYD3, IFITM1, IFITM3, SLCO2A1, CNR1, TMEM30B, AXIN2, PRIMA1, ERCC6L, TMEM97, TESC, PODXL, MET, ITGA2, SPPL2A, ABCB1, DIO2, SLC7A1, CPNE1, SLC13A2, RHBDL2, HSPD1, LRRC8E, CLDN8, ACOX1, CLDN5, AMN, LGR6, RHOU, LGR5, GSN, ATP8B1, MGLL, ANO5, KIF14, SGK1, PARM1, TRPM6, PTGER4, MPP6, PIGR, LDLRAD3, PRKCB, SLC41A2, CA4, CLDN2, CNTN4, CA2, CNTN3, JAM2, GAP43, PMEPA1, CPM, PPP1R12B, TRIB3, CDH3, MTM1, CAMK2D, PLCD1, NEDD4L, SCNN1G, SCNN1B, FGFBP1, SECTM1, PLP1, CR2, SLC12A2, RGS13, GCG, RNF43, SLCO1B3, SLC6A6, SMPD1, LIPH, DSC2, SLC5A6, SMPD3 Novel prognosis biomarkers and drugs for colorectal cancer 5

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term -value Genes AURKA, SELENBP1, CCT2, PTTG1, ACTG2, SULT1A1, WDR77, SULT1A2, FAS, CDCA5, KIF13B, CDCA3, RAN, BYSL, EIF2S3, GLTP, FARP1, GRB10, MAD2L1, PGM5, SULT1B1, TACSTD2, NME1, PGM1, KIF4A, AHCY, NEK2, CHEK1, DENND2A, IGF2BP3, PPAT, EPHB1, GPD1L, CDA, OSBPL3, NUF2, GGH, HGD, ACACB, GART, SFRP1, NTRK2, FERMT1, ANPEP, SPINK5, CKB, HSPH1, LMOD1, MYC, CDC6, POLR1D, EXOSC5, TPX2, GZMB, POLR1C, CCT6A, RRM2, PFDN4, LTV1, EIF5A2, BID, SORD, FHL1, NOB1, HK2, UGDH, TXLNG, ZBTB16, HMMR, DGKA, NCAPG, BCL2, BUB1, PRKAA2, PAPSS2, PHLDA1, PLA2G16, NAT1, NAT2, CAPN2, PCK1, TP53RK, GBA3, CCNB1, EEF1E1, MT2A, PSAT1, HPGD, PAICS, TP53INP2, CEP72, RNASEL, PRC1, IL18, ADH1C, IQGAP2, ADH1B, PMAIP1, SLC7A5, ITPKA, CMBL, GOTERM_CC_DIRECT GO:0005829~cytosol 2.41e-06 PRKAR2B, CDKN2B, ANK2, TIAM1, PRKACB, TGS1, DNAJC2, NANP, DARS, STAP2, PDE4D, PLCE1, TRIM36, RIOK3, AKR1B10, VSNL1, PDE5A, RIPK2, AKAP7, XDH, SRI, EIF4E3, GNE, CLU, CTPS2, SPC25, EIF3B, CSE1L, NPM1, AXIN2, ERCC6L, FGD4, XPOT, TSR1, RPGRIP1L, CPNE1, MYH11, FABP4, FABP1, RPL37A, AHCYL2, HSPD1, PDZD3, MYLK, FABP6, KIF23, PINK1, CAD, RHOU, PRMT3, KIF2C, TP53I3, DES, PLCB4, GSN, SDPR, CASP7, MGLL, PLCB1, AKR1C1, PPP1R14A, KIF14, CDK1, SGK1, SGK2, PADI2, KIF16B, UBE2C, CDK4, ECT2, PRKCB, PRDX6, CA7, BUB1B, PDE9A, CA2, CA1, UGP2, HAUS6, PHLPP2, NDN, PPP1R12B, SYNC, PRKDC, TRIB3, ALDH1A1, MTM1, HSPA2, PAFAH1B3, CAMK2D, PLCD1, NEDD4L, GEMIN5, GSTA1, CENPN, PNO1, KIF18A, CENPF, CDC25B, RGS13, CENPH, CADPS, SCGN, DUS4L PRC1, THRB, XPO4, DBF4, CBX4, SYNCRIP, CBX2, AURKA, MCM10, ISG20, KLHL7, CDCA7, CDKN2B, WDR77, DDX21, PRKACB, NUP35, TGS1, DNAJC2, CDCA5, CCNA2, PID1, VWA5A, DTL, RAN, BYSL, ENC1, RNASEH2A, GRHL1, PPARGC1A, NCAPD3, MRTO4, RCL1, RFC3, GTF2IRD1, DSCC1, SRI, FGFR2, KIF4A, SOX4, CHEK1, ANLN, SOX9, ZC3H8, EIF3B, CSE1L, NCAPG2, C4ORF19, OSBPL1A, TEAD4, NPM1, AXIN2, ERCC6L, XPOT, GINS1, NKRF, KLF9, TSR1, ARID3A, ATAD2, HEATR1, NOLC1, GTF2F2, SYTL4, WDR3, FABP1, RAD54B, FBXO32, GO:0005654~ THNSL1, UTP14A, UTP20, HDAC9, RPP40, KLF4, KIF23, GTF3A, ACOX1, GOTERM_CC_DIRECT 0.002742 nucleoplasm CPT2, TAF1A, CDC14A, E2F5, TAF1D, E2F7, EZH2, CAD, HSPH1, DCAF13, HPSE, FANCI, CASP7, MGLL, MYC, TOP2A, CDK1, CDC6, SGK1, POLR1D, EXOSC5, TPX2, LEF1, POLR1C, POLR1B, MCM2, UBE2C, CDK4, MCM4, PRKCB, TRAP1, RRM2, IPO5, RUVBL1, ADAM12, LTV1, WDR43, PMEPA1, UBE2T, PEG3, CKS1B, HAUS6, USP2, ETHE1, PPP1R12B, NR3C2, NOB1, UGDH, POLA1, ZNF367, PRKDC, TRIB3, NR3C1, C2ORF88, BUB1, CAMK2D, WDR12, HS6ST2, PRKAA2, NEDD4L, ETV4, FEN1, SIM2, GEMIN5, KLK6, CENPN, KAT2B, MSH2, PNO1, PAK1IP1, CENPF, CDC25B, CENPH, TP53RK, CCNB1, PHF19, CCDC113, NR5A2, HPGD, TEX10, KIF20A TSPAN1, SYNCRIP, TTK, SELENBP1, NFXL1, SLC7A5, CBFB, HS2ST1, ELOVL5, ST3GAL4, DDX21, FAS, CFI, GTPBP4, DARS, RAN, STMN2, BYSL, PDE4D, METTL7A, IL11RA, NCAPD3, GLTP, VSIG2, CD36, NME1, TACSTD2, VSNL1, EFNA5, FGFR2, SRI, KIF4A, GCNT3, GCNT2, MAMDC2, IFITM1, TFCP2L1, PNPT1, FXYD5, GPR143, SLCO2A1, CSE1L, BCHE, NCAPG2, NPM1, B3GNT6, SLC28A2, ERCC6L, LAPTM4B, MGAT4A, OSBPL3, MKI67, SCD, NUF2, ATP11A, SPPL2A, ABCB1, ENDOD1, HEATR1, GO:0016020~ MUC4, PLEKHA8, DIO2, SLC7A1, SYTL4, CPNE1, SLC13A2, SYTL2, HSPD1, GOTERM_CC_DIRECT 6.13e-04 membrane FABP6, ACOX1, PRPH, ACVRL1, PINK1, CAD, SLC26A2, BZW2, KIF2C, IMMP2L, SRPX, FANCI, HPSE, MGLL, SLC22A3, LMOD1, FAM129A, CEACAM1, KIF14, KCNMA1, ABCE1, CDK1, EGFL6, MPP6, GZMB, IL6R, MCM4, SLC26A3, TRAP1, PRDX6, IPO5, CA4, LRMP, RUVBL1, PDCD2L, BID, RERGL, SORD, HK2, PRKDC, CEP55, CDH3, HMMR, DGKA, HSPA2, NCAPG, BCL2, CAMK2D, BUB1, PAFAH1B3, ACSL6, FEN1, GEMIN5, SLC12A2, MSH2, ATP1A2, CCNB1, TP53RK, SLC17A4, PLN, SLC5A6, LRP8, PAICS, VLDLR, RETSAT 6 Sun Z et al. J Biomed Res, 2020, 1(0)

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term P-value Genes EDN3, CTHRC1, GLDN, IL18, MMP7, SELENBP1, MMP3, CXCL11, CXCL12, ACTG2, AZGP1, OGN, REG3A, PTGIS, TGFBI, MS4A1, COL12A1, CFI, CFD, TGS1, MTUS1, SPON1, CLCA1, STC2, SPARCL1, PTPRR, C10ORF99, TCN1, PRELP, SCGB2A1, CD36, TACSTD2, COL1A2, COL1A1, WFDC2, XDH, WNT5A, CLU, CHEK1, CCL5, GREM2, ABI3BP, SIAE, ANGPTL1, DEFB1, GO:0005615~ OLFM1, BMP4, BMP2, CFB, PODXL, EFEMP1, GGH, CHI3L1, MUC4, TST, GOTERM_CC_DIRECT 3.05e-09 extracellular space C2ORF40, CEL, LAMA1, TNFSF10, SRPX2, SFRP1, SFRP2, PYY, HSPD1, TPSAB1, BMP7, SST, MUC5B, PLAU, IGFBP6, ANPEP, AMN, CKB, SMPDL3A, GSN, GPX3, DPEP1, GHR, EGFL6, CILP, IL6R, PIGR, CHGA, PTGDS, PRDX6, FRMD4B, CA2, CXCL1, CPM, SORD, CXCL5, CXCL3, CXCL2, CCL28, AGT, PCSK9, C2, THBS1, FGFBP1, SCG2, DPT, KLK6, SECTM1, CES2, CCL19, GCG, FBLN1, SMPD1, LIPH, GDF15 EDN3, INSL5, FAM3D, IL18, IGFBP6, MMP7, MMP3, CXCL11, CXCL12, SPINK5, DNASE1L3, MMP1, OGN, HSPH1, AZGP1, GSN, RSPO3, GPX3, TGFBI, COL12A1, KLK10, GUCA2A, CFI, CFD, COL11A1, COL10A1, GHR, STC2, C10ORF99, IL6R, TCN1, MMP12, PCOLCE2, PRELP, INHBA, CHRDL1, PTGDS, COL1A2, EFNA5, CNTN4, COL1A1, MFAP4, ADAM12, GO:0005576~ GOTERM_CC_DIRECT 0.006199 CHGB, MFAP5, WFDC2, VIP, WNT5A, FGFR2, CXCL1, IL1R2, C7, CXCL5, extracellular region CXCL3, CLU, CXCL2, ESM1, CCL5, CCL28, GREM2, EPHB1, GLIPR2, PROCR, BCHE, AGT, CDA, C2, THBS1, DEFB1, FGFBP1, NMU, KLK6, BMP4, BMP2, COL4A1, CFB, MET, DHRS11, EFEMP1, CCL19, GCG, CEL, SCGN, LAMA1, FBLN1, TNFSF10, SFRP1, SFRP2, LIPH, LRP8, PYY, TPSAB1, BMP7, GDF15, SST, PLAU LRRC8E, ACVRL1, TSPAN1, TSPAN3, AQP8, SLC6A20, TSPAN5, TSPAN7, ANPEP, LPAR1, LGR6, VIPR1, APCDD1, SLC26A2, SLC7A5, LGR5, ZNRF3, EDNRA, AGTR1, CD44, CD46, MS4A1, ATP8B1, SLC22A3, FAS, SLC22A5, SLC4A4, CEACAM1, PAG1, MUC12, GHR, CLCA1, PTGER4, CLCA4, SLCO4A1, PTPRH, SLC22A23, LIFR, PIGR, SSPN, IL11RA, SLC26A3, VSIG2, GO:0005887~integral CD36, SSTR1, TACSTD2, PTGDR, CLDN1, GPA33, LRMP, JAM2, FGFR2, GOTERM_CC_DIRECT component of plasma 3.78e-04 SLC2A13, FXYD3, SLC39A10, ENPP3, CACNB2, FXYD5, EPHB1, BEST4, membrane SLCO2A1, BEST2, PROCR, LY6E, CNR1, SCNN1G, SCNN1B, SLC28A2, DCLK1, TMPRSS2, SLC12A2, PODXL, MET, NPY1R, MUC4, CD1D, SLCO1B3, CEL, SEMA6A, EPHA4, RNF43, TNFSF10, PROM2, SEMA6D, ADCY9, SLC17A4, ATP2A3, SLC7A1, NTRK2, SLC6A6, SLC13A2, SLC5A6, SCARA5 ACOX1, CPT2, E2F5, LYAR, SELENBP1, MCM10, ISG20, WDR74, KLHL7, DCAF13, URB2, DDX21, TGS1, TOP2A, MYC, GTPBP4, DTL, RAN, BYSL, EXOSC5, ENC1, TOP1MT, POLR1B, CDK4, MRTO4, ACADVL, RCL1, NOP2, GO:0005730~ GOTERM_CC_DIRECT 7.32e-04 IPO5, DDX31, WDR43, NEK2, POLA1, TRIB3, NUFIP1, PRKDC, ZBTB16, nucleolus NPM1, BRIX1, WDR12, ARNTL2, RBM28, FEN1, ETV4, PHLDA1, NKRF, KLK6, CCDC86, MKI67, TSR1, PAK1IP1, PNO1, ARID3A, HEATR1, RPF2, NOLC1, GPATCH2, WDR3, UTP20, UTP14A, TEX10 TSPAN1, USP2, GALNT6, ENPP3, CLU, SYNC, PINK1, AURKA, ITM2C, GO:0048471~ SPINK5, PRKAR2B, MT1E, CAMK2D, PCSK9, TMEM100, PRKACB, MT1H, GOTERM_CC_DIRECT perinuclear region of 0.012382 MT1G, MT1F, GTPBP4, PLA2G16, MT1M, STC2, STMN2, PTPRR, CHI3L1, cytoplasm CENPF, ITGA2, CDK4, CDKN3, MT1X, INHBA, CHGA, MAD2L1, PTGDS, DGAT2, NME1, PLN, MT2A, CA4, BUB1B, PDE9A FGFR2, WNT5A, CPM, ACVRL1, CLU, MMP7, IQGAP2, LPAR1, HMMR, SRPX, HSPA2, CD44, PROCR, CD46, PCSK9, FAS, THBS1, FGFBP1, GO:0009986~cell GOTERM_CC_DIRECT 0.006327 CEACAM1, GHR, C10ORF54, BMP2, CAPN5, MET, ITGA2, ABCB1, IL6R, surface CD1D, CEL, EPHA4, CD36, PROM2, SFRP1, SRPX2, CA4, GPA33, HSPD1, SCARA5, PLAU SHROOM4, SLC6A20, GPR143, NHS, AMN, SLC7A5, ANK2, ATP8B1, GO:0016324~apical SCNN1G, SLC22A5, SCNN1B, DPEP1, CEACAM1, RAB27A, KCNMA1, GOTERM_CC_DIRECT 4.36e-06 plasma membrane TRPM6, MYO1A, SLC12A2, CLCA4, PODXL, CDHR2, SI, ABCB1, CDHR5, PDE4D, IL6R, SLC26A3, CD36, PROM2, SLC17A4, CLDN1, CA4, AKAP7 KIF23, CEP72, HAUS6, CDC14A, NDN, USP2, NEK2, GNAI1, NIT2, CHEK1, GO:0005813~ AURKA, CEP55, PRKAR2B, DCAF13, PROCR, NCAPG, NPM1, RANBP1, GOTERM_CC_DIRECT 0.004323 centrosome PRKACB, AXIN2, ERCC6L, CKAP2, CDK1, DTL, RPGRIP1L, CENPF, PDE4D, HEPACAM2, CDC25B, CCNB1, NME1, SYTL4, WDR43 Novel prognosis biomarkers and drugs for colorectal cancer 7

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term P-value Genes FGFR2, CLU, MMP7, PRKDC, CCT2, EDIL3, ABI3BP, MMP1, OGN, TGFBI, GO:0031012~ COL12A1, THBS1, SPON1, DPT, COL4A1, RAN, EFEMP1, CILP, CCT6A, GOTERM_CC_DIRECT 4.15e-05 extracellular matrix PRELP, LAMA1, FBLN1, SFRP1, SFRP2, ZG16, COL1A2, COL1A1, HSPD1, BMP7, MFAP4, TPSAB1 WNT5A, CTHRC1, MAMDC2, GLDN, MMP7, MMP28, MMP3, MMP1, OGN, GO:0005578~ HPSE, TGFBI, COL11A1, COL10A1, SPON1, DPT, BMP4, SPARCL1, GOTERM_CC_DIRECT proteinaceous 1.10e-04 EFEMP1, CHI3L1, CILP, MMP12, MUC4, PRELP, LAMA1, FBLN1, SFRP1, extracellular matrix ZG16, COL1A2 KLK6, TMEM97, GTPBP4, OSBPL3, DTL, TRIB3, TXLNG, CDK4, MRTO4, GO:0031965~nuclear GOTERM_CC_DIRECT 0.018467 PTGDS, ATP2A3, BCL2, IPO5, WDR3, PLCB1, NUP35, DNAJC2, TEX10, membrane RETSAT GO:0045121~ GNAI1, ITLN1, PODXL, ARID3A, CAPN2, EPHB1, PRKAR2B, MALL, PROM2, GOTERM_CC_DIRECT 0.027858 membrane raft CD36, ANK2, HPSE, SDPR, CNR1, HSPD1, FAS, PAG1 KIF23, KIF14, CDK1, KIF4A, PRC1, RAN, GNAI1, NEK2, CENPF, AURKA, GOTERM_CC_DIRECT GO:0030496~midbody 0.002377 HEPACAM2, CEP55, ECT2, ASPM, KIF20A KIF23, HAUS6, PRC1, TPX2, CENPF, NEDD9, TTK, CBX3, AURKA, NR3C1, GOTERM_CC_DIRECT GO:0005819~spindle 0.003653 HEPACAM2, PTP4A1, MTUS1, KIF20A LDHD, SYNCRIP, SELENBP1, CITED2, WDR74, AGTR1, OGN, MALL, WDR77, FAS, GNG4, CDCA5, CCNA2, RAB27A, CDCA3, PCID2, PTPRH, C16ORF62, CDHR2, PTPRR, LIFR, EIF2S3, CDHR5, PROX1, GLTP, NCAPD3, GRB10, NME1, ZNF239, IL1R2, KIF4A, PPP2R3A, AHCY, GNAI1, CACNB2, PROCR, DUSP14, NCAPG2, TMEM123, LAPTM4B, CCDC86, MKI67, NUF2, ATP11A, HGD, ACACB, FNBP1, NOLC1, SYTL4, SYTL2, FCGBP, LIMA1, TAF1A, LXN, TAF1D, EZH2, NAP1L2, RNF183, SMPDL3A, SLC22A3, SLC22A5, TMEM100, MYC, DPEP1, CEACAM1, GHR, CDC6, EXOSC5, TPX2, CCT6A, IL6R, MXD1, EPB41L3, INHBA, CLIC5, RRM2, PFDN4, CYBRD1, RUVBL1, WDR43, EIF5A2, NKD1, ALPI, TBC1D9, FHL1, POLA1, HK2, NUFIP1, C2ORF88, CCL28, ITM2C, ITM2A, BUB1, PCSK9, WDR12, MT1H, FEN1, MT1G, PHLDA1, MT1F, TRIP13, CCNB1IP1, TMPRSS2, SHMT2, PAK1IP1, NPY1R, CAPN2, APPL2, MT1X, CCNB1, PHF19, PLSCR4, DUSP1, PLN, ZG16, MT2A, LRP8, NR5A2, RNASEL, TSPAN1, PRC1, SLC6A20, XPO4, IL18, CXCL11, CBFB, PRKAR2B, AZGP1, ANK2, CDKN2B, NUDCD1, ELOVL5, TGFBI, DDX21, SPON1, POU2AF1, STMN2, ENC1, STAP2, PDE4D, MRTO4, AKR1B10, VSNL1, COL1A2, DDX31, COL1A1, NFE2L3, MFAP4, UGGT2, DCUN1D5, IFITM1, PPIL1, IFITM3, BEX1, CTPS2, CCL5, MEIS1, OSBPL1A, TEAD4, TMEM30B, HELLS, ERCC6L, MUC2, MET, EFEMP1, ARID3A, SPPL2A, ABCB1, TNFSF10, SLC7A1, GTF2F2, MYH11, RPL37A, FABP1, FBXO32, HSPD1, HDAC9, TPSAB1, MS4A12, PDZD3, CLDN8, LRRC8E, KIF23, E2F5, CDC14A, FIGNL1, E2F6, LYAR, E2F7, PINK1, RHOU, PRMT3, KIF2C, DES, CASP7, SNTB1, AKR1C1, KIF14, CDK1, TRPM6, SGK1, PTGER4, CDK4, PRDX6, SLC41A2, IPO5, CLDN1, CLDN2, CA4, PDE9A, CA2, JAM2, CA1, CASQ2, UGP2, PMEPA1, GAP43, VIP, PHLPP2, NR3C2, NR3C1, GRAMD3, MSX2, GO:0005515~protein HSPA2, PAFAH1B3, GPSM2, SCNN1G, NEDD4L, SCNN1B, KLK6, PLP1, GOTERM_MF_DIRECT 5.56e-05 binding COL4A1, SLC12A2, C1ORF21, DACH1, CDC25B, CADPS, GCG, CCDC113, SMPD1, DSC2, GDF15, CCT2, PTPN21, AURKA, PTTG1, LPAR1, ZNRF3, C1ORF109, CD44, CD46, SULT1A1, SULT1A2, CFI, NUP35, COL10A1, KIF13B, GTPBP4, RAN, BYSL, PPARGC1A, RFC3, NOP2, CD36, MAD2L1, CGN, SULT1B1, TACSTD2, PGM1, HHLA2, CHGB, NEK2, CHEK1, KRT20, IGF2BP3, GPR143, EPHB1, C4ORF19, CDA, SKA3, OLFM1, NKRF, BMP4, BMP2, OSBPL3, LGALS2, HOMER1, ABCG2, LAMA1, EPHA4, CEL, SEMA6A, SRPX2, SFRP1, RAD54B, PYY, UTP20, UTP14A, AGR3, BMP7, PLAU, KLF4, ACVRL1, CKB, EDNRA, HSPH1, FANCI, GPX3, FAM129A, TOP2A, KCNMA1, ABCE1, POLR1D, GZMB, POLR1C, ARRDC4, POLR1B, SLC26A3, TRAP1, STYK1, PTGDS, PTGDR, GPA33, LTV1, BID, USP2, CXCL2, ZBTB16, FAM46A, FAM46C, HMMR, GPM6A, CD177, NCAPG, AGT, BCL2, PRKAA2, THBS1, NMU, ETV4, PLA2G16, TBX3, DLGAP5, NAT2, SYNPO2, ATP1A2, CDKN3, TP53RK, SLC16A9, EEF1E1, SAMD9, PAICS, TP53INP2, TEX10, KIF20A, VLDLR, BCAR3, TEX11, CEP72, THRB, CBX4, TTK, CBX3, CBX2, PMAIP1, VIPR1, MCM10, MMP3, KLHL7, REG3A, PTGIS, MYOCD, TIAM1, SLC25A23, ARL14, MS4A1, PRKACB, SLC4A4, TGS1, PAG1, PID1, DARS, DTL, SLC22A23, CHP2, SOCS6, NEBL, ASB9, PLCE1, TRIM36, RIOK3, RIPK2, AKAP7, DSCC1, SRI, WNT5A, FGFR2, GNE, PNPT1, CLU, SOX4, NEDD9, SOX9, ZC3H8, SPC25, EIF3B, CSE1L, NPM1, ENTPD5, AXIN2, DEFB1, TMEM97, TESC, PODXL, RPGRIP1L, ITGA2, HEATR1, KCTD9, CPNE1, AHCYL2, MUC5B, MYLK, PRPH, LGR6, LGR5, FAM83D, PLCB4, TMEM171, GSN, HPSE, SDPR, ATP8B1, PLCB1, BTNL8, MPP6, LEF1, MCM2, HEPACAM2, UBE2C, MCM4, ECT2, PRKCB, FAM134B, BUB1B, CKS1B, KRT6B, PPP1R12B, PRKDC, TRIB3, CEP55, MTM1, CAMK2D, CNN1, FGFBP1, GEMIN5, SCG2, SYNPO, KAT2B, MSH2, KIF18A, CENPF, CCDC68, CENPH, RNF43, CKS2, SYNM 8 Sun Z et al. J Biomed Res, 2020, 1(0)

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term P-value Genes RNASEL, TTK, AURKA, CCT2, ITPKA, ACTG2, DDX21, DDX10, PRKACB, KIF13B, DARS, C10ORF2, RIOK3, NME1, RIPK2, DDX31, FGFR2, ABCA8, KIF4A, GNE, NEK2, CHEK1, CTPS2, EPHB1, HELLS, ERCC6L, MYO1A, MKI67, MET, ATAD2, ATP11A, ABCB1, ACACB, GART, ABCG2, EPHA4, NOLC1, ATP2A3, GTF2F2, NTRK2, MYH11, RAD54B, HSPD1, MYLK, KIF23, GO:0005524~ATP GOTERM_MF_DIRECT 8.92e-04 ACVRL1, FIGNL1, PINK1, CAD, CKB, KIF2C, HSPH1, ATP8B1, SLC22A5, binding TOP2A, KIF14, ABCE1, CDC6, CDK1, TRPM6, SGK1, SGK2, TPX2, MCM2, KIF16B, CCT6A, CDK4, UBE2C, MCM4, PRKCB, TRAP1, STYK1, BUB1B, RUVBL1, UBE2T, HK2, TRIB3, PRKDC, ITM2C, DGKA, HSPA2, CKMT2, CAMK2D, BUB1, PRKAA2, PAPSS2, ACSL6, DCLK1, TRIP13, MSH2, PDK4, KIF18A, ATP1A2, TP53RK, ADCY9, PAICS, KIF20A CKS1B, ACVRL1, PRC1, PPP1R12B, POLA1, TRIB3, AURKA, FAM83D, GO:0019901~protein CDKN2B, ANK2, NPM1, AXIN2, CCNA2, GHR, KIF13B, KIF14, KAT2B, GOTERM_MF_DIRECT 0.010768 kinase binding SLC12A2, MSH2, PTPRR, TPX2, CDC25B, CCNB1, CADPS, TRAP1, NME1, CKS2, AKAP7, KIF20A EZH2, POLA1, CBX4, CBX2, NAP1L2, SOX9, MEIS1, CITED2, PRKAA2, GO:0003682~ DNAJC2, TOP2A, CDCA5, HELLS, CDK1, SHMT2, KAT2B, RAN, ARID3A, GOTERM_MF_DIRECT 0.017367 chromatin binding LEF1, ATAD2, CENPF, NCAPD3, PRKCB, PLAC8, CKS2, FABP1, NR5A2, UBE2T, TEX10 FGFR2, CKS1B, GNE, FGGY, PDK4, TRIB3, PINK1, PRKDC, CHEK1, GO:0016301~kinase GOTERM_MF_DIRECT 0.002215 CDKN3, CKB, DGKA, PRKAR2B, CDKN2B, CKMT2, NTRK2, BUB1, RIPK2, activity AKAP7, PRKAA2, PRKACB, MYLK, PLAU GO:0008201~heparin BMP4, FGFR2, LXN, CCDC80, MMP7, CXCL11, GREM2, ABI3BP, PRELP, GOTERM_MF_DIRECT 0.001381 binding PCOLCE2, CEL, OGN, SFRP1, RSPO3, LIPH, THBS1, BMP7, FGFBP1 ABCA8, SLCO4A1, AQP8, ABCB1, SLCO2A1, ABCG2, SLC26A3, SLCO1B3, GO:0005215~ GOTERM_MF_DIRECT 0.028378 PTGDS, CPNE1, SLC22A3, FABP4, SLC13A2, SLC5A6, FABP1, FABP6, transporter activity KIF20A GO:0016491~ SQRDL, SORD, HSD17B2, MAOA, SCD, DHRS11, MAOB, ADH1C, ADH1B, GOTERM_MF_DIRECT 0.049408 oxidoreductase activity ALDH1A1, TP53I3, RRM2, ETFDH, HPGD, AKR1C1, RETSAT GO:0016887~ATPase ABCA8, KIF14, KIF23, ABCE1, MSH2, CLU, ATAD2, ATP1A2, ABCG2, GOTERM_MF_DIRECT 0.049162 activity KIF2C, RFC3, RUVBL1, HSPD1, KIF13B, KIF20A GO:0046983~protein E2F5, E2F6, POLR1D, POLR1C, HES6, MXD1, ASCL2, TCF21, TCFL5, HPSE, GOTERM_MF_DIRECT 0.024082 dimerization activity ANO5, ARNTL2, MYC, CEACAM1 GO:0005179~hormone GOTERM_MF_DIRECT 0.012518 VIP, GCG, EDN3, INHBA, INSL5, STC2, AGT, GUCA2A, PYY, SST, CHGB activity GO:0005200~ FRMD3, EPB41L3, DES, KRT6B, ANK2, EPB41L4A, TUBAL3, SYNM, GOTERM_MF_DIRECT structural constituent 0.033582 EPB41L4B, KRT20, VILL of cytoskeleton GO:0005201~ LAMA1, FBLN1, COL4A1, COL1A2, CHI3L1, COL1A1, COL11A1, MFAP5, GOTERM_MF_DIRECT extracellular matrix 0.003889 MUC5B, PRELP structural constituent GO:0008009~ GOTERM_MF_DIRECT 0.001836 CXCL1, CXCL5, CXCL3, CXCL2, CCL19, CCL5, CXCL11, CXCL12, CCL28 chemokine activity GO:0005254~chloride GOTERM_MF_DIRECT 0.00345 BEST2, SLC26A3, FXYD3, CLCA1, CLCA4, CLIC5, CLIC6, SLC26A2, BEST4 channel activity GO:0050660~flavin GOTERM_MF_DIRECT adenine dinucleotide 0.009754 ACADVL, XDH, FMO5, ACOX1, ACADS, LDHD, MAOB, ETFDH, DUS4L binding GO:0017080~sodium GOTERM_MF_DIRECT channel regulator 5.81e-04 GPD1L, SGK1, FXYD3, SGK2, AGT, NEDD4L, FXYD5, TMPRSS3 activity GO:0003712~ GOTERM_MF_DIRECT transcription cofactor 0.048083 MSX2, SLC26A3, POU2AF1, KAT2B, HES6, MXD1, CBFB, TRIP13 activity

Novel prognosis biomarkers and drugs for colorectal cancer 9

Supplementary Table 2 Top 20 terms of GO and KEGG analysis of the overlap DEGs on DAVID (continued) Category Term P-value Genes GO:0004435~ phosphatidylinositol GOTERM_MF_DIRECT 0.001319 EDNRA, PLCL2, PLCE1, PLCB4, PLCD1, CCL5, PLCB1 phospholipase C activity GO:0001786~ GOTERM_MF_DIRECT phosphatidylserine 0.006963 SDPR, SCIN, CPNE1, SYTL2, PLCD1, THBS1, GAP43 binding ACOX1, B3GALT5, PTGS1, ADH1C, ADH1B, CAD, ANPEP, ITPKA, CMBL, CKB, ST6GALNAC6, PTGIS, PLCB4, ST3GAL4, HPSE, MGLL, PLCB1, NANP, POLR1D, ACADS, DHRS9, POLR1C, POLR1B, ST6GALNAC1, ACADVL, PLCE1, DGAT2, PTGDS, PRDX6, NME1, AKR1B10, RRM2, PGM1, UGP2, hsa01100:Metabolic XDH, GCNT3, ALPI, GCNT2, SORD, AHCY, HSD17B2, GNE, GALNT6, KEGG_PATHWAY 0.013592 pathways ENPP3, POLA1, UGDH, HK2, CTPS2, PPAT, ALDH1A1, DGKA, MTM1, CKMT2, B3GNT6, PAFAH1B3, CDA, PLCD1, UGT2A3, GALNT12, PAPSS2, ACSL6, MGAT4A, SHMT2, PLA2G16, MAOA, NAT1, SI, MAOB, NAT2, HGD, ACACB, PCK1, GART, GBA3, TST, CEL, GGT6, HMGCS2, SMPD1, AHCYL2, PSAT1, PAICS, SMPD3 FGFR2, WNT5A, BID, CKS1B, GNAI1, GNA11, LPAR1, ZBTB16, CXCL12, hsa05200:Pathways in MMP1, EDNRA, AGTR1, PLCB4, CDKN2B, BCL2, FAS, PRKACB, AXIN2, KEGG_PATHWAY 0.006456 cancer PLCB1, GNG4, MYC, BMP4, BMP2, COL4A1, PTGER4, MSH2, MET, LEF1, ITGA2, CDK4, PRKCB, LAMA1, ADCY9, CKS2 CDC6, CDK1, CDC14A, E2F5, DBF4, TTK, PRKDC, CHEK1, PTTG1, MCM2, KEGG_PATHWAY hsa04110:Cell cycle 2.89e-05 CDK4, MCM4, CDC25B, CCNB1, MAD2L1, CDKN2B, BUB1, BUB1B, MYC, CCNA2 XDH, POLR1D, ENPP3, PNPT1, POLA1, POLR1C, PDE4D, POLR1B, PPAT, hsa00230:Purine KEGG_PATHWAY 0.006106 GART, ADCY9, NME1, RRM2, PGM1, PDE5A, ENTPD5, PDE9A, PAPSS2, metabolism PAICS hsa04972:Pancreatic KCNMA1, CLCA1, CLCA4, SLC12A2, ATP1A2, PRKCB, CEL, SLC26A3, KEGG_PATHWAY 0.001281 secretion PLCB4, ADCY9, ATP2A3, CA2, SLC4A4, PLCB1 hsa04919:Thyroid BMP4, KAT2B, THRB, ATP1A2, RCAN2, PRKCB, PLCE1, PLCB4, DIO2, PLN, KEGG_PATHWAY hormone signaling 0.008328 PLCD1, PRKACB, PLCB1, MYC pathway hsa04310:Wnt WNT5A, NKD1, MMP7, LEF1, PRKCB, PLCB4, SFRP1, SFRP2, CAMK2D, KEGG_PATHWAY 0.033427 signaling pathway RUVBL1, PRKACB, AXIN2, PLCB1, MYC hsa04270:Vascular EDNRA, KCNMA1, ACTG2, AGTR1, PLCB4, ADCY9, GNA11, PPP1R12B, KEGG_PATHWAY smooth muscle 0.022479 PRKACB, PLCB1, MYLK, PPP1R14A, PRKCB contraction IL1R2, MUC2, LAMA1, COL4A1, PLCB4, GNA11, COL1A2, PRKACB, KEGG_PATHWAY hsa05146:Amoebiasis 0.026124 COL1A1, PLCB1, COL11A1, PRKCB hsa04978:Mineral SLC26A3, TRPM6, MT1M, MT2A, CYBRD1, MT1E, ATP1A2, MT1H, MT1X, KEGG_PATHWAY 8.40e-05 absorption MT1G, MT1F hsa04924:Renin EDNRA, KCNMA1, AGTR1, CLCA1, PLCB4, PTGER4, CLCA4, GNAI1, AGT, KEGG_PATHWAY 0.001967 secretion PRKACB, PLCB1 hsa04971:Gastric acid PLCB4, ADCY9, GNAI1, CAMK2D, PRKACB, ATP1A2, CA2, PLCB1, SST, KEGG_PATHWAY 0.005259 secretion MYLK, PRKCB hsa00240:Pyrimidine NME1, POLR1D, RRM2, PNPT1, POLA1, ENTPD5, CDA, CTPS2, POLR1C, KEGG_PATHWAY 0.043588 metabolism CAD, POLR1B hsa03320:PPAR KEGG_PATHWAY 0.009022 ACOX1, CPT2, CD36, SCD, FABP4, FABP1, ACSL6, MMP1, FABP6, PCK1 signaling pathway hsa04115:p53 KEGG_PATHWAY 0.009022 BID, CCNB1, CDK1, TP53I3, RRM2, CHEK1, FAS, PMAIP1, THBS1, CDK4 signaling pathway hsa04911:Insulin KCNMA1, GCG, PLCB4, ADCY9, GNA11, CAMK2D, PRKACB, ATP1A2, KEGG_PATHWAY 0.037569 secretion PLCB1, PRKCB hsa04970:Salivary BEST2, KCNMA1, PLCB4, SLC12A2, ADCY9, PRKACB, ATP1A2, PLCB1, KEGG_PATHWAY 0.040065 secretion MUC5B, PRKCB hsa04640:Hematopoiet KEGG_PATHWAY 0.042671 IL1R2, CD36, CR2, CD44, MS4A1, ITGA2, ANPEP, IL6R, IL11RA, CD1D ic cell lineage hsa03008:Ribosome RCL1, GTPBP4, RAN, NOB1, WDR3, HEATR1, UTP14A, WDR43, RBM28, KEGG_PATHWAY biogenesis in 0.042671 RPP40 eukaryotes hsa04512:ECM- LAMA1, CD36, COL4A1, CD44, COL1A2, ITGA2, COL1A1, THBS1, COL11A1, KEGG_PATHWAY 0.042671 receptor interaction HMMR