Identification of the Hub Genes Associated with the Prognosis of Ovarian Cancer Patients via Integrated Bioinformatics Analysis and Experimental Validation

References

• Kahn LG, Philippat C, Nakayama SF, Slama R, Trasande L. Endocrine-disrupting chemicals: implications for human health. Lancet Diabetes Endocrinol. 2020;8(8):703–718. doi:10.1016/S2213-8587(20)30129-732707118
   PubMed Web of Science ®Google Scholar
• Sessa C, Schneider DT, Planchamp F, et al. ESGO-SIOPE guidelines for the management of adolescents and young adults with non-epithelial ovarian cancers. Lancet Oncol. 2020;21(7):e360–e368. doi:10.1016/S1470-2045(20)30091-732615119
   PubMed Web of Science ®Google Scholar
• Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240–1253. doi:10.1016/S0140-6736(18)32552-230910306
   PubMed Web of Science ®Google Scholar
• Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384(9951):1376–1388. doi:10.1016/S0140-6736(13)62146-724767708
   PubMed Web of Science ®Google Scholar
• Rojas V, Hirshfield KM, Ganesan S, Rodriguez-Rodriguez L. Molecular characterization of epithelial ovarian cancer: implications for diagnosis and treatment. Int J Mol Sci. 2016;17:12. doi:10.3390/ijms17122113
   Web of Science ®Google Scholar
• Deo A, Mukherjee S, Rekhi B, Ray P. Subtype specific biomarkers associated with chemoresistance in epithelial ovarian cancer. Indian J Pathol Microbiol. 2020;63(Supplement):S64–s69. doi:10.4103/IJPM.IJPM_872_1932108633
   PubMed Web of Science ®Google Scholar
• Yang H, Cui W, Wang L. Epigenetic synthetic lethality approaches in cancer therapy. Clin Epigenetics. 2019;11(1):136. doi:10.1186/s13148-019-0734-x31590683
   PubMed Web of Science ®Google Scholar
• Zelli V, Compagnoni C, Cannita K, et al. Applications of next generation sequencing to the analysis of familial breast/ovarian cancer. High-Throughput. 2020;9:1. doi:10.3390/ht9010001
   PubMedGoogle Scholar
• Winterhoff BJ, Maile M, Mitra AK, et al. Single cell sequencing reveals heterogeneity within ovarian cancer epithelium and cancer associated stromal cells. Gynecol Oncol. 2017;144(3):598–606. doi:10.1016/j.ygyno.2017.01.01528111004
   PubMed Web of Science ®Google Scholar
• Zhang L, Luo M, Yang H, Zhu S, Cheng X, Qing C. Next-generation sequencing-based genomic profiling analysis reveals novel mutations for clinical diagnosis in Chinese primary epithelial ovarian cancer patients. J Ovarian Res. 2019;12(1):19. doi:10.1186/s13048-019-0494-430786925
   PubMed Web of Science ®Google Scholar
• Zhang K, Kong X, Feng G, et al. Investigation of hypoxia networks in ovarian cancer via bioinformatics analysis. J Ovarian Res. 2018;11(1):16. doi:10.1186/s13048-018-0388-x29482638
   PubMed Web of Science ®Google Scholar
• Li W, Liu Z, Liang B, et al. Identification of core genes in ovarian cancer by an integrative meta-analysis. J Ovarian Res. 2018;11(1):94. doi:10.1186/s13048-018-0467-z30453999
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang X, Fan S, Zhang Z. Identification of modules and hub genes associated with platinum-based chemotherapy resistance and treatment response in ovarian cancer by weighted gene co-expression network analysis. Medicine. 2019;98(44):e17803. doi:10.1097/MD.000000000001780331689861
   PubMed Web of Science ®Google Scholar
• Yang D, He Y, Wu B, et al. Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer. J Ovarian Res. 2020;13(1):10. doi:10.1186/s13048-020-0613-231987036
   PubMed Web of Science ®Google Scholar
• Reimand J, Kull M, Peterson H, Hansen J, Vilo J. g: Profiler–aweb-based toolset for functional profiling of gene lists from large-scale experiments. Nucleic Acids Res. 2007;35(WebServer issue):W193–200. doi:10.1093/nar/gkm22617478515
   PubMed Web of Science ®Google Scholar
• Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(Suppl 4):S11. doi:10.1186/1752-0509-8-S4-S1125521941
   PubMed Web of Science ®Google Scholar
• Gyorffy B, Lánczky A, Szállási Z. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012;19(2):197–208. doi:10.1530/ERC-11-032922277193
   PubMed Web of Science ®Google Scholar
• Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–w102. doi:10.1093/nar/gkx24728407145
   PubMed Web of Science ®Google Scholar
• Alcaraz-Sanabria A, Nieto-Jiménez C, Corrales-Sánchez V, et al. Synthetic lethality interaction between aurora kinases and chek1 inhibitors in ovarian cancer. Mol Cancer Ther. 2017;16(11):2552–2562. doi:10.1158/1535-7163.MCT-17-022328847989
   PubMed Web of Science ®Google Scholar
• Wang C, Yan Q, Hu M, Qin D, Feng Z. Effect of AURKA gene expression knockdown on angiogenesis and tumorigenesis of human ovarian cancer cell lines. Target Oncol. 2016;11(6):771–781. doi:10.1007/s11523-016-0436-727250762
   PubMed Web of Science ®Google Scholar
• Feng H, Gu ZY, Li Q, Liu QH, Yang XY, Zhang JJ. Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis. J Ovarian Res. 2019;12(1):35. doi:10.1186/s13048-019-0508-231010415
   PubMed Web of Science ®Google Scholar
• Zhang L, Sun L, Zhang B, Chen L. Identification of differentially expressed genes (DEGS) relevant to prognosis of ovarian cancer by use of integrated bioinformatics analysis and validation by immunohistochemistry assay. Medical Science Monitor. 2019;25:9902–9912. doi:10.12659/MSM.92166131871312
   PubMed Web of Science ®Google Scholar
• Chong T, Sarac A, Yao CQ, et al. Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer. J Ovarian Res. 2018;11(1):27. doi:10.1186/s13048-018-0399-729618387
   PubMed Web of Science ®Google Scholar
• Kao GD, McKenna WG, Yen TJ. Detection of repair activity during the DNA damage-induced G2 delay in human cancer cells. Oncogene. 2001;20(27):3486–3496. doi:10.1038/sj.onc.120444511429695
   PubMed Web of Science ®Google Scholar
• Ghisoni E, Maggiorotto F, Borella F, et al. TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers. J Ovarian Res. 2019;12(1):17. doi:10.1186/s13048-019-0492-630760286
   PubMed Web of Science ®Google Scholar
• Zhang R, Xu J, Zhao J, Bai JH. Proliferation and invasion of colon cancer cells are suppressed by knockdown of TOP2A. J Cell Biochem. 2018;119(9):7256–7263. doi:10.1002/jcb.2691629761838
   PubMed Web of Science ®Google Scholar
• Ma HT, Poon RYC. Aurora kinases and DNA damage response. Mutat Res. 2020;821:111716. doi:10.1016/j.mrfmmm.2020.11171632738522
   PubMed Web of Science ®Google Scholar
• Do TV, Xiao F, Bickel LE, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene. 2014;33(5):539–549. doi:10.1038/onc.2012.63223334327
   PubMed Web of Science ®Google Scholar
• Yang H, Ou CC, Feldman RI, Nicosia SV, Kruk PA, Cheng JQ. Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells. Cancer Res. 2004;64(2):463–467. doi:10.1158/0008-5472.CAN-03-290714744757
   PubMed Web of Science ®Google Scholar
• Yang G, Chang B, Yang F, et al. Aurora kinase A promotes ovarian tumorigenesis through dysregulation of the cell cycle and suppression of BRCA2. Clinical Cancer Res. 2010;16(12):3171–3181. doi:10.1158/1078-0432.CCR-09-317120423983
   PubMed Web of Science ®Google Scholar
• Lassmann S, Shen Y, Jütting U, et al. Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy. Clinical Cancer Res. 2007;13(14):4083–4091. doi:10.1158/1078-0432.CCR-06-277517634533
   PubMed Web of Science ®Google Scholar
• Yang F, Guo X, Yang G, Rosen DG, Liu J. AURKA and BRCA2 expression highly correlate with prognosis of endometrioid ovarian carcinoma. Modern Pathol. 2011;24(6):836–845. doi:10.1038/modpathol.2011.44
   PubMed Web of Science ®Google Scholar
• Mignogna C, Staropoli N, Botta C, et al. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients. J Ovarian Res. 2016;9(1):31. doi:10.1186/s13048-016-0238-727209210
   PubMed Web of Science ®Google Scholar
• Wan X, Yeung C, Kim SY, et al. Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma. Cancer Res. 2012;72(22):5889–5899. doi:10.1158/0008-5472.CAN-12-199123002205
   PubMed Web of Science ®Google Scholar
• Baker DJ, Jeganathan KB, Cameron JD, et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet. 2004;36(7):744–749. doi:10.1038/ng138215208629
   PubMed Web of Science ®Google Scholar
• Kops GJ, Foltz DR, Cleveland DW. Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint. Proc Natl Acad Sci U S A. 2004;101(23):8699–8704. doi:10.1073/pnas.040114210115159543
   PubMed Web of Science ®Google Scholar
• Chen H, Lee J, Kljavin NM, et al. Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma. Genes Cancer. 2015;6(3–4):106–118. doi:10.18632/genesandcancer.5326000094
   PubMedGoogle Scholar
• Kawakubo E, Matsumoto T, Yoshiya K, et al. BUBR1 insufficiency is correlated with enos reduction experimentally in vitro and in vivo, and in gastric cancer tissue. Anticancer Res. 2018;38(11):6099–6106. doi:10.21873/anticanres.1296030396924
   PubMed Web of Science ®Google Scholar
• Yamamoto Y, Matsuyama H, Chochi Y, et al. Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. Cancer Genet Cytogenet. 2007;174(1):42–47. doi:10.1016/j.cancergencyto.2006.11.01217350465
   PubMedGoogle Scholar
• Fu X, Chen G, Cai ZD, et al. Overexpression of BUB1B contributes to progression of prostate cancer and predicts poor outcome in patients with prostate cancer. Onco Targets Ther. 2016;9:2211–2220. doi:10.2147/OTT.S10199427143916
   PubMed Web of Science ®Google Scholar
• Sun Q, Zhao H, Zhang C, et al. Gene co-expression network reveals shared modules predictive of stage and grade in serous ovarian cancers. Oncotarget. 2017;8(26):42983–42996. doi:10.18632/oncotarget.1778528562334
   PubMedGoogle Scholar
• Rattner JB, Rao A, Fritzler MJ, Valencia DW, Yen TJ. CENP-F is a.ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization. Cell Motil Cytoskeleton. 1993;26(3):214–226. doi:10.1002/cm.9702603057904902
   PubMed Web of Science ®Google Scholar
• Sun J, Huang J, Lan J, et al. Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell Int. 2019;19:264. doi:10.1186/s12935-019-0986-831632198
   PubMed Web of Science ®Google Scholar
• Shahid M, Kim M, Lee MY, et al. Downregulation of CENPF remodels prostate cancer cells and alters cellular metabolism. Proteomics. 2019;19(11):e1900038. doi:10.1002/pmic.20190003830957416
   PubMed Web of Science ®Google Scholar
• Kim HE, Kim DG, Lee KJ, et al. Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PLoS One. 2012;7(8):e43223. doi:10.1371/journal.pone.004322322912832
   PubMed Web of Science ®Google Scholar
• Xu Z, Zhou Y, Cao Y, Dinh TL, Wan J, Zhao M. Identification of candidate biomarkers and analysis of prognostic values in ovarian cancer by integrated bioinformatics analysis. Medical Oncology. 2016;33(11):130. doi:10.1007/s12032-016-0840-y27757782
   PubMed Web of Science ®Google Scholar
• Yeganeh PN, Richardson C, Bahrani-Mostafavi Z, Tait DL, Mostafavi MT. Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade serous ovarian cancer from both normal epithelia and benign tumor tissues. Genes Cancer. 2017;8(11–12):784–798. doi:10.18632/genesandcancer.16429321820
   PubMedGoogle Scholar
• Lee JH, Berger JM. Cell cycle-dependent control and roles of DNA topoisomerase II. Genes. 2019;10:11. doi:10.3390/genes10110859
   Web of Science ®Google Scholar
• Chen T, Sun Y, Ji P, Kopetz S. Topoisomerase IIα in chromosome instability and personalized cancer therapy. Oncogene. 2015;34(31):4019–4031. doi:10.1038/onc.2014.33225328138
   PubMed Web of Science ®Google Scholar
• Gao Y, Zhao H, Ren M, et al. TOP2A promotes tumorigenesis of high-grade serous ovarian cancer by regulating the tgf-β/smad pathway. J Cancer. 2020;11(14):4181–4192. doi:10.7150/jca.4273632368301
   PubMed Web of Science ®Google Scholar
• Kucukgoz Gulec U, Gumurdulu D, Guzel AB, et al. Prognostic importance of survivin, Ki-67, and topoisomerase IIα in ovarian carcinoma. Arch Gynecol Obstet. 2014;289(2):393–398. doi:10.1007/s00404-013-3000-z23974278
   PubMed Web of Science ®Google Scholar
• Rath O, Kozielski F. Kinesins and cancer. Nat Rev Cancer. 2012;12(8):527–539. doi:10.1038/nrc331022825217
   PubMed Web of Science ®Google Scholar
• Schneider MA, Christopoulos P, Muley T, et al. AURKA, DLGAP5, TPX2, KIF11 and CKAP5: five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients. Int J Oncol. 2017;50(2):365–372. doi:10.3892/ijo.2017.383428101582
   PubMed Web of Science ®Google Scholar
• Zhou J, Chen WR, Yang LC, et al. KIF11 functions as an oncogene and is associated with poor outcomes from breast cancer. Cancer Research Treatment. 2019;51(3):1207–1221. doi:10.4143/crt.2018.46030590004
   PubMed Web of Science ®Google Scholar
• Venere M, Horbinski C, Crish JF, et al. The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma. Sci Transl Med. 2015;7(304):304ra143. doi:10.1126/scitranslmed.aac6762
   PubMed Web of Science ®Google Scholar
• Takenaga M, Yamamoto Y, Takeuchi T, et al. Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor. Biochem Biophys Res Commun. 2015;463(3):222–228. doi:10.1016/j.bbrc.2015.05.02925998394
   PubMed Web of Science ®Google Scholar
• Shi B, Bao J, Liu Y, Shi J. Death receptor 6 promotes ovarian cancer cell migration through KIF11. FEBS Open Bio. 2018;8(9):1497–1507. doi:10.1002/2211-5463.12492
   PubMed Web of Science ®Google Scholar
• Liu J, Meng H, Li S, et al. Identification of potential biomarkers in association with progression and prognosis in epithelial ovarian cancer by integrated bioinformatics analysis. Front Genet. 2019;10:1031. doi:10.3389/fgene.2019.0103131708970
   PubMed Web of Science ®Google Scholar
• Engqvist H, Parris TZ, Kovács A, et al. Validation of novel prognostic biomarkers for early-stage clear-cell, endometrioid and mucinous ovarian carcinomas using immunohistochemistry. Front Oncol. 2020;10:162. doi:10.3389/fonc.2020.0016232133296
   PubMed Web of Science ®Google Scholar
• Li T, Li Y, Gan Y, et al. Methylation-mediated repression of MiR-424/503 cluster promotes proliferation and migration of ovarian cancer cells through targeting the hub gene KIF23. Cell Cycle. 2019;18(14):1601–1618. doi:10.1080/15384101.2019.162411231135262
   PubMed Web of Science ®Google Scholar