Table 3.
Genetic networks in CT drugs-treated OC spheroidsa.
| Ntwk | Genes in Ingenuity networksb | Associated pathways | Scorec |
| A. Networks, commonly affected by treatment with all drugs (cisplatin, topotecan and paclitaxel) | |||
| 1 | ARL2, ARL6IP, ATAD2, BUB1 (includes EG:699), CDKN1A, CEP55, CTH, DEAF1, DTL, EIF5A, FHIT, HES6, HIST1H1B, HNRPA2B1, HOXA10, ING5, KIAA0101, KIF23, KIF2C, NUSAP1, PBK, PKMYT1, PLK1, PRC1, PSAP, RACGAP1, SORT1, SPDEF, TBCD, TUBB3, TUBB2A, UBE2S, UBE2T, UHRF1, VGLL4 | Cell Cycle, Cellular Movement, Cancer | 43 |
| 2 | BIRC3, BRE, CASP3, CASP7, CEBPE, CSF3, CTSD, DLC1, DNM2, EDA, EIF4B, EIF4G1, EMD, ENO1, FADD, FANCA, GPX4, GRK1, IGF2R, IL17RA, KNTC2, LAMA5, LMNA, MAD1L1, PLSCR1, PRKCE, PTMA, RHO, SNCG, SPBC25, SPTAN1, TNFRSF6B, TRIM63, TXNL5, ZWINT | Cell Death, Connective Tissue Disorders, Cellular Growth and Proliferation | 43 |
| 3 | ADCY2, AHR, ALCAM, APOE, ASCL2, CASK, CCND1, CDKN2D, COX7A2L, CRYL1, DBP, DKK1, DLG1, DLL4, F11R, FZD1, FZD4, GMNN, KLF5, LDLR, LDLRAP1, LRPAP1, MCM10, MDFI (includes EG:4188), MRAS, PER2, PLXNB2, PPP2CB, PPP2R4, SET, SMARCB1, SMARCD2, SNX17 (includes EG:9784), WNT1, WNT3A | Gene Expression, Lipid Metabolism, Small Molecule Biochemistry | 43 |
| 4 | AKT2, BRCA1, BRCA2, C5, CA5A, CD151, DDB2, DDIT4, GNB2L1, HMG20B, IFI35, ITGB1, ITGB1BP2, JAK1, LRCH4, NMI, NOV, NRAS, NTN1, PERP (includes EG:64065), PIK4CA, PITPNM1, PPP1R2, PPP1R9B, PTPN11, PTPRM, SERPINH1, SH2D1A (includes EG:4068), SLAMF1, SLC7A8, SNAI2, TMED9, TNFAIP2 (includes EG:7127), XRCC6, YWHAB | Cell Death, Cancer, Cell Cycle | 43 |
| 5 | ACAA1, ACOT8, B2M, CTSL2, DHCR24, GADD45B, HIPK2, HLA-A, HLA-B, HLA-E, HLA-F, HMGA1, IL22RA2, INSR, MGLL, MVK, MYBBP1A, NALP12, PCNA, PFDN6, PIK3R2, PKLR, POLDIP2, PPARA, PPARGC1B, PSMB8, PTPRG, RFX1, RFXAP, RRM1, SFRS5, SNX15, SURF6, TOMM40, TUB | Nutritional Disease, Cancer, Lipid Metabolism | 43 |
| B. Networks, affected by cisplatin treatment | |||
| 1 | BRCA1, CEBPE, CLU, DDIT4, ECE1, EEF1D, ENO1, EPPB9, GATA3, HIPK2, LDLR, LDLRAP1, LTBP3, MAD1L1, MAPKAPK2, MGMT, MSH2, MXD4, PDZK1IP1, PERP (includes EG:64065), PKIG, PLSCR1, PRKCG, PSMC3, PSMD12, RAG2, RHO, SMAD3, SPHK1, STOML2, TGFB1, TGIF, TMEPAI, TNFAIP2 (includes EG:7127), XRCC6 | Cell Cycle, Cancer | 51 |
| 2 | ATAD2, CDC2, CDKN1A, CHAF1B, DKFZP762E1312, DNMT1, DTL, EXO1, FHIT, HES6, HOXA10, ING5, KIAA0101, MCM2, MCM3, MCM4, MCM10, MYBBP1A, NUSAP1, PBK, PCNA, PIP5K1C, PKMYT1, PSAP, RACGAP1, RRM1, RRM2, RUVBL2, TYMS, UBE2A (includes EG:7319), UBE2S, UBE2T, UHRF1, VGLL4, WDHD1 | DNA Replication, Recombination, and Repair, Cancer | 51 |
| 3 | APAF1, APIP, AVEN, BCL2A1, BDNF, BIN1, BIRC1, CASP3, CASP7, CSH2, CTSD, DBNL, DEDD, DFFA, DLC1, DNM2, EIF4G1, EIF4G3, FADD, GAS2, GPX4, HCRT, HSH2D, ITGB3BP, LTBR, MAP2K5, PDE4A, PINK1, PRKAA2, PRKCZ, PSAP, SNCG, STK11, TGFA, TNFRSF6B | Cell Death, Cancer, Hematological Disease | 21 |
| 4 | BRD2, C19ORF2, CREB1, CYP11A1, EP300, EWSR1, EXOSC6, FUSIP1, GAS2L1, HLA-G, HSPA4L, ITM2C, LSM7, MYH13, MYOD1, NFYB, NUDT2, POLR1A, POLR2A, POLR2E, POLR2F, RRN3, SENP1, SIAHBP1, SUPT3H, TAF1C, TBP, TEAD2, TEAD4, TKT, TNNC1, TNNI2, TNNT2, TRERF1, VGLL1 | Gene Expression, Cell Cycle, Skeletal and Muscular System Development and Function | 20 |
| 5 | ALAS1, ALPP, ARPC5, CD244, CD2BP2, CTH, CUGBP2, DNAJB5, EDF1, EGR2, EPS8L2, ERG, FOS, GRM4, HDLBP, HLA-B, HOXA9, IL1RL1, JUB, JUN, KEAP1, NFE2L2, NIPSNAP1, NTS (includes EG:57303), PMP22, RPS9, SDCBP, SKIV2L, SNCG, SNRPB, SOS1, USP1, WBP4, WDR90, WT1 | Gene Expression, Organismal Injury and Abnormalities | 18 |
| C. Networks, affected by topotecan treatment | |||
| 1 | ARL6IP, ASPM, ATAD2, CDKN1A, COG1, COG5, CRI2, DDB2, DEAF1, DLG7, FHIT, H2AFZ, HES6, HIST1H1B, HNRPA2B1, KIF2C, KLF5, LIG3, MLLT1, NEIL1, NUSAP1, PARP2, PLK2, PSAP, RACGAP1, SET, SPDEF, SUPT16H, TRIM44 (includes EG:54765), UBE2C, UBE2D1, UBE2S, UBE2T, UHRF1, VGLL4 | DNA Replication, Recombination, and Repair, Cell Cycle, Cellular Compromise | 41 |
| 2 | ADCY2, ADCY5, AKT1, ASCL2, CCL19, CCND1, CDH2, DKK1, DLC1, DLG1, DLG2, DLL4, FZD1, FZD4, GNAI1, GNB1, GNB2L1, H2AFX, MDFI (includes EG:4188), MRAS, NEUROG1, NEUROG3, NRAS, PRKAG1, PRKAR1A, PTPRM, RASSF1, ROBO1, SEMA3C, SRGAP1, TBCD, TUBB3, TUBB2A, WNT1, WNT3A | Cellular Movement, Cancer, Reproductive System Disease | 41 |
| 3 | AMPH, BRE, CABIN1, CALM1, CASP3, DAPK1, DDEF1, DNM2, DOCK1, EIF4B, EIF4G1, EIF4G3, ENO1, EPN1, EPS15, GNLY, GRK1, LMNA, MAP4K3, PTK2, PTMA, RHO, RIT2, SNCG, SPHK1, SPTAN1, SPTBN1, STK3, SYNE2, TNFRSF6B, TPD52L1, TPD52L2, TRIO, TXNL5, WASF1 | Cellular Assembly and Organization, Cellular Function and Maintenance, Cellular Movement | 41 |
| 4 | ALDOA, ANP32B, B2M, BRF1, CALR, CAMK1, CKB, CLIC4, CORO1A, ELAVL1, FN1, GABARAP, HLA-A, HLA-B, HLA-E, IGF1R, ITGB5, ITGB3BP, ITSN1, KPNA2, KRT8, MAPK7, MEF2A, NALP12, NTN1, NUMB, PTPN11, PTPN3 (includes EG:5774), RAB1A, RAN, SLC2A4RG, SND1 (includes EG:27044), VCL, YWHAB, ZAK | Protein Trafficking, Cell Death, Molecular Transport | 41 |
| 5 | ACTL6A, ACTL6B, ARID1B (includes EG:57492), CCNB2, CDC2, CDK8, CEP170, CGA, CTSL2, GMNN, HMGA2, IFITM2, IFNGR1, INSR, ISGF3G, JAK1, MED25, NEK2, PKMYT1, PLK1, PLXNB2, PRKCZ, PSMA4, PSMB7, PTPRG, PTTG1, RAD51AP1, RNF103, SFRS5, SLC9A3R1, SMARCB1, SMARCD2, SNX15, SURF6, TUB | Cell Cycle, Cellular Assembly and Organization, Cancer | 41 |
| D. Networks, affected by paclitaxel treatment | |||
| 1 | BAG5, CTNNB1, CTNNBIP1, FZD8, GSTP1 (includes EG:2950), H2-ALPHA, JRK, K-ALPHA-1, KIF23, KLK2, LOC112714, LRP6, MDFI (includes EG:4188), MRPL13, MT3, MYF5, PARK2, PLK1, PTP4A3, RBP4, SERPINA5, TPT1, TUBA1, TUBA2, TUBA3, TUBA6, TUBA8, TUBB, TUBB1, TUBB3, TUBB4, TUBB2A, TUBB2C, TUBG1, WNT3A | Cancer, Reproductive System Disease, Renal and Urological Disease | 22 |
| 2 | ALOX5AP, ASAH2, CEBPE, CEBPG, DDIT3, DHPS, DNAJB5, DUSP9 (includes EG:1852), EIF4G1, ELK4, ERN1 (includes EG:2081), G6PD, GCLC, GCLM, IL3, IMPDH2, LAT, LCN2, MAPK12, MKNK1, MKNK2, MMP8, MT2A, NFE2L2, PRG2 (includes EG:5553), RPS6KA5 (includes EG:9252), SLC5A5, SLK, TALDO1, TDRD7, TGIF, TLR9, TNF, WNT10A, ZBTB17 | Drug Metabolism, Molecular Transport, Small Molecule Biochemistry | 19 |
| 3 | ARPC1A, ARPC1B, BAX, BIRC6, CCNL2, CXCL13, DDIT4, EIF5A, FFAR3, GATA3, GPR44, HLA-A, HLA-E, HNRPA2B1, HOXC11, HSD17B1, ING5, JMY, LETMD1, LMNA, LTB, LTBP1, MDH1, MDM4, NALP12, PEG3 (includes EG:5178), PPP1R13B, PYCARD, RALY, SERPINB5, STK11, TBX21, TP53, TP53INP1, VHL | Cancer, Cell Death, Skeletal and Muscular Disorders | 19 |
| 4 | AHNAK, ANP32B, BAK1, C19ORF10, CAMP, DBP, DDIT3, ELAVL1, ENO2, FCGR2A, FCGR2B, HLA-C, HNRPA2B1, HRAS, IFI202B, IFNG, IL6, IL24, IL1RL1, LGALS1, LY6E, MOG, PLCE1, PSMB9, PSMB10, PTMA, S100A10, SDHA, SIRPA, TAP1, TFG, TNFRSF10B, TNFRSF6B, TRIM21, TTC28 | Connective Tissue Disorders, Inflammatory Disease, Cell Death | 17 |
| 5 | ATF6, ATP5B, BZRAP1, COL1A1, COX4I2, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX7A2L, COX7B, COX8C, CREBL1, DBI, GATAD2B, HDAC1 (includes EG:3065), ITM2C, LY6A, MBD3 (includes EG:53615), MBD3L1, MRPL12, MT1A, MYC, NFYB, PLK1, PRRG2, RAB3D, RIMS1, RIMS2, TRAM2, TSPO, TXNIP, UBE2S, ZBTB16 | Cancer, Gene Expression, Tumor Morphology | 17 |
aThe five top-scoring networks for each drug treatment are presented.
bBold genes are those identified by the microarray analysis, other genes were either not on the expression array or excluded by our gene expression selection criteria.
cA score of 3 was considered significant (p < 0.001).