Skip to main content
Top
Published in: Journal of Ovarian Research 1/2018

Open Access 01-12-2018 | Research

Identification of core genes in ovarian cancer by an integrative meta-analysis

Authors: Wenyu Li, Zheran Liu, Bowen Liang, Siyang Chen, Xinping Zhang, Xiaoqin Tong, Weiming Lou, Lulu Le, Xiaoli Tang, Fen Fu

Published in: Journal of Ovarian Research | Issue 1/2018

Login to get access

Abstract

Background

Epithelial ovarian cancer is one of the most severe public health threats in women. Since it is still challenging to screen in early stages, identification of core genes that play an essential role in epithelial ovarian cancer initiation and progression is of vital importance.

Results

Seven gene expression datasets (GSE6008, GSE18520, GSE26712, GSE27651, GSE29450, GSE36668, and GSE52037) containing 396 ovarian cancer samples and 54 healthy control samples were analyzed to identify the significant differentially expressed genes (DEGs). We identified 563 DEGs, including 245 upregulated and 318 downregulated genes. Enrichment analysis based on the gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the upregulated genes were significantly enriched in cell division, cell cycle, tight junction, and oocyte meiosis, while the downregulated genes were associated with response to endogenous stimuli, complement and coagulation cascades, the cGMP-PKG signaling pathway, and serotonergic synapse. Two significant modules were identified from a protein-protein interaction network by using the Molecular Complex Detection (MCODE) software. Moreover, 12 hub genes with degree centrality more than 29 were selected from the protein-protein interaction network, and module analysis illustrated that these 12 hub genes belong to module 1. Furthermore, Kaplan-Meier analysis for overall survival indicated that 9 of these hub genes was correlated with poor prognosis of epithelial ovarian cancer patients.

Conclusion

The present study systematically validates the results of previous studies and fills the gap regarding a large-scale meta-analysis in the field of epithelial ovarian cancer. Furthermore, hub genes that could be used as a novel biomarkers to facilitate early diagnosis and therapeutic approaches are evaluated, providing compelling evidence for future genomic-based individualized treatment of epithelial ovarian cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Desai A, Xu J, Aysola K, et al. Epithelial ovarian cancer: an overview. World J Transl Med. 2014;3(1):1-8.CrossRef Desai A, Xu J, Aysola K, et al. Epithelial ovarian cancer: an overview. World J Transl Med. 2014;3(1):1-8.CrossRef
2.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRef Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.CrossRef
3.
go back to reference Bast RC Jr, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9(6):415.CrossRef Bast RC Jr, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009;9(6):415.CrossRef
4.
go back to reference Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018;81:17–38.CrossRef Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018;81:17–38.CrossRef
5.
go back to reference Banno K, Yanokura M, Iida M, et al. Application of MicroRNA in diagnosis and treatment of ovarian cancer. Biomed Res Int. 2014;2014(3):232817.CrossRef Banno K, Yanokura M, Iida M, et al. Application of MicroRNA in diagnosis and treatment of ovarian cancer. Biomed Res Int. 2014;2014(3):232817.CrossRef
6.
go back to reference Agarwal R, Kaye SB. Ovarian cancer: Strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3:502–16.CrossRef Agarwal R, Kaye SB. Ovarian cancer: Strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3:502–16.CrossRef
7.
go back to reference Norouzi-Barough L, Sarookhani MR, Sharifi M, Moghbelinejad S, Jangjoo S, Salehi R. Molecular mechanisms of drug resistance in ovarian cancer. J Cell Physiol. 2018;233:4546–62.CrossRef Norouzi-Barough L, Sarookhani MR, Sharifi M, Moghbelinejad S, Jangjoo S, Salehi R. Molecular mechanisms of drug resistance in ovarian cancer. J Cell Physiol. 2018;233:4546–62.CrossRef
8.
go back to reference Lech A, Daneva T, Pashova S, Gagov H, Crayton R, Kukwa W, et al. Ovarian cancer as a genetic disease. Front Biosci. 2013;18:543–63.CrossRef Lech A, Daneva T, Pashova S, Gagov H, Crayton R, Kukwa W, et al. Ovarian cancer as a genetic disease. Front Biosci. 2013;18:543–63.CrossRef
9.
go back to reference An J, Lv W, Zhang Y. LncRNA NEATI contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEBI expression via miR-194. Onco Targets Ther. 2017;10:5377–90.CrossRef An J, Lv W, Zhang Y. LncRNA NEATI contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEBI expression via miR-194. Onco Targets Ther. 2017;10:5377–90.CrossRef
10.
go back to reference Morgan RD, Clamp AR, Evans DGR, Edmondson RJ, Jayson GC. PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer. Cancer Chemother Pharmacol. 2018;81:647–58.CrossRef Morgan RD, Clamp AR, Evans DGR, Edmondson RJ, Jayson GC. PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer. Cancer Chemother Pharmacol. 2018;81:647–58.CrossRef
11.
go back to reference Vetter MH, Hays JL. Use of targeted therapeutics in epithelial ovarian cancer: a review of current literature and future directions. Clin Ther. 2018;40:361–71.CrossRef Vetter MH, Hays JL. Use of targeted therapeutics in epithelial ovarian cancer: a review of current literature and future directions. Clin Ther. 2018;40:361–71.CrossRef
12.
go back to reference Johnson N, Liao JB. Novel therapeutics for ovarian cancer: the 11th Biennial Rivkin Center Ovarian cancer Research Symposium. Int J Gynecol Cancer. 2017;27(9S):S14–9.CrossRef Johnson N, Liao JB. Novel therapeutics for ovarian cancer: the 11th Biennial Rivkin Center Ovarian cancer Research Symposium. Int J Gynecol Cancer. 2017;27(9S):S14–9.CrossRef
13.
go back to reference Spies M, Dasu MRK, Svrakic N, Nesic O, Barrow RE, Perez-Polo JR, et al. Gene expression analysis in burn wounds of rats. Am J Physiol Regul Integr Comp Physiol. 2002;283(4):R918–30.CrossRef Spies M, Dasu MRK, Svrakic N, Nesic O, Barrow RE, Perez-Polo JR, et al. Gene expression analysis in burn wounds of rats. Am J Physiol Regul Integr Comp Physiol. 2002;283(4):R918–30.CrossRef
14.
15.
go back to reference Cheung HW, Cowley GS, Weir BA, Boehm JS, Rusin S, Scott JA, et al. Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc Natl Acad Sci. 2011;108(30):12372–7.CrossRef Cheung HW, Cowley GS, Weir BA, Boehm JS, Rusin S, Scott JA, et al. Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer. Proc Natl Acad Sci. 2011;108(30):12372–7.CrossRef
16.
go back to reference Chee M, Yang R, Hubbell E, et al. Accessing genetic information with high-density DNA arrays. Science. 1996;274(5287):610–4.CrossRef Chee M, Yang R, Hubbell E, et al. Accessing genetic information with high-density DNA arrays. Science. 1996;274(5287):610–4.CrossRef
17.
go back to reference Vaughan S, Coward JI, Bast RC Jr, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719.CrossRef Vaughan S, Coward JI, Bast RC Jr, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719.CrossRef
18.
go back to reference Hong F, Breitling R, McEntee CW, Wittner BS, Nemhauser JL, Chory J. RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics. 2006;22(22):2825–7.CrossRef Hong F, Breitling R, McEntee CW, Wittner BS, Nemhauser JL, Chory J. RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics. 2006;22(22):2825–7.CrossRef
19.
go back to reference Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(D1):D447–52.CrossRef Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43(D1):D447–52.CrossRef
20.
go back to reference Scardoni G, Tosadori G, Faizan M, et al. Biological network analysis with CentiScaPe: centralities and experimental dataset integration. F1000Res. 2015;139(3):1-9. Scardoni G, Tosadori G, Faizan M, et al. Biological network analysis with CentiScaPe: centralities and experimental dataset integration. F1000Res. 2015;139(3):1-9.
21.
go back to reference Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM, Howlader N, et al. Annual report to the nation on the Status of Cancer, part I: National cancer statistics. Cancer. 2018;124(13):2785-800.CrossRef Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM, Howlader N, et al. Annual report to the nation on the Status of Cancer, part I: National cancer statistics. Cancer. 2018;124(13):2785-800.CrossRef
22.
go back to reference Di Men C, Liu QN, Ren Q. A prognostic 11 genes expression model for ovarian cancer. J Cell Biochem. 2018;119(2):1971–8.CrossRef Di Men C, Liu QN, Ren Q. A prognostic 11 genes expression model for ovarian cancer. J Cell Biochem. 2018;119(2):1971–8.CrossRef
23.
go back to reference Previs RA, Sood AK, Mills GB, Westin SN. The rise of genomic profiling in ovarian cancer. Expert Rev Mol Diagn. 2016;16:1337–51.CrossRef Previs RA, Sood AK, Mills GB, Westin SN. The rise of genomic profiling in ovarian cancer. Expert Rev Mol Diagn. 2016;16:1337–51.CrossRef
24.
go back to reference Lindqvist A, Rodríguez-Bravo V, Medema RH. The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol. 2009;185:193–202.CrossRef Lindqvist A, Rodríguez-Bravo V, Medema RH. The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol. 2009;185:193–202.CrossRef
25.
go back to reference Diril MK, Ratnacaram CK, Padmakumar VC, Du T, Wasser M, Coppola V, et al. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci. 2012;109(10):3826–31.CrossRef Diril MK, Ratnacaram CK, Padmakumar VC, Du T, Wasser M, Coppola V, et al. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci. 2012;109(10):3826–31.CrossRef
26.
go back to reference Xi Q, Huang M, Wang Y, Zhong J, Liu R, Xu G, et al. The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer. Tumor Biol. 2015;36(7):4939–48.CrossRef Xi Q, Huang M, Wang Y, Zhong J, Liu R, Xu G, et al. The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer. Tumor Biol. 2015;36(7):4939–48.CrossRef
27.
go back to reference Md AS, Md S, Mazharol HM, et al. Inhibition of DNA topoisomerase type IIα(TOP2A) by mitoxantrone and its halogenated derivatives: a combined density functional and molecular docking study. Biomed Res Int. 2016;2016(5):12. Md AS, Md S, Mazharol HM, et al. Inhibition of DNA topoisomerase type IIα(TOP2A) by mitoxantrone and its halogenated derivatives: a combined density functional and molecular docking study. Biomed Res Int. 2016;2016(5):12.
28.
go back to reference Zhou Z, Liu S, Zhang M, Zhou R, Liu J, Chang Y, et al. Overexpression of topoisomerase 2-alpha confers a poor prognosis i pancreatic adenocarcinoma identified by co-expression analysis. Dig Dis Sci. 2017;62(10):2790–800.CrossRef Zhou Z, Liu S, Zhang M, Zhou R, Liu J, Chang Y, et al. Overexpression of topoisomerase 2-alpha confers a poor prognosis i pancreatic adenocarcinoma identified by co-expression analysis. Dig Dis Sci. 2017;62(10):2790–800.CrossRef
29.
go back to reference Ito F, Furukawa N, Nakai T. Evaluation of TOP2A as a predictive marker for endometrial cancer with taxane-containing adjuvant chemotherapy. Int J Gynecol Cancer. 2016;26(2):325–30.CrossRef Ito F, Furukawa N, Nakai T. Evaluation of TOP2A as a predictive marker for endometrial cancer with taxane-containing adjuvant chemotherapy. Int J Gynecol Cancer. 2016;26(2):325–30.CrossRef
30.
go back to reference Erriquez J, Becco P, Olivero M, Ponzone R, Maggiorotto F, Ferrero A, et al. TOP2A gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin. Gynecol Oncol. 2015;138(3):627–33.CrossRef Erriquez J, Becco P, Olivero M, Ponzone R, Maggiorotto F, Ferrero A, et al. TOP2A gene copy gain predicts response of epithelial ovarian cancers to pegylated liposomal doxorubicin. Gynecol Oncol. 2015;138(3):627–33.CrossRef
31.
go back to reference Chen T, Sun Y, Ji P, Kopetz S, Zhang W. Topoisomerase IIalpha in chromosome instability and personalized cancer therapy. Oncogene. 2015;34(31):4019–31.CrossRef Chen T, Sun Y, Ji P, Kopetz S, Zhang W. Topoisomerase IIalpha in chromosome instability and personalized cancer therapy. Oncogene. 2015;34(31):4019–31.CrossRef
32.
go back to reference Yamaguchi M, VanderLinden R, Weissmann F, Qiao R, Dube P, Brown NG, et al. Cryo-EM of mitotic checkpoint complex-bound APC/C reveals reciprocal and conformational regulation of ubiquitin ligation. Mol Cell. 2016;63(4):593–607.CrossRef Yamaguchi M, VanderLinden R, Weissmann F, Qiao R, Dube P, Brown NG, et al. Cryo-EM of mitotic checkpoint complex-bound APC/C reveals reciprocal and conformational regulation of ubiquitin ligation. Mol Cell. 2016;63(4):593–607.CrossRef
33.
go back to reference Xie C, Powell C, Yao M, et al. Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker. Int J Biochem Cell Biol. 2014;47:113–7.CrossRef Xie C, Powell C, Yao M, et al. Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker. Int J Biochem Cell Biol. 2014;47:113–7.CrossRef
34.
go back to reference Rape M, Reddy SK, Kirschner MW. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell. 2006;124(1):89–103.CrossRef Rape M, Reddy SK, Kirschner MW. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell. 2006;124(1):89–103.CrossRef
35.
go back to reference Van Ree JH, Jeganathan KB, Malureanu L, Van Deursen JM. Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation. J Cell Biol. 2010;188(1):83–100.CrossRef Van Ree JH, Jeganathan KB, Malureanu L, Van Deursen JM. Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation. J Cell Biol. 2010;188(1):83–100.CrossRef
Metadata
Title
Identification of core genes in ovarian cancer by an integrative meta-analysis
Authors
Wenyu Li
Zheran Liu
Bowen Liang
Siyang Chen
Xinping Zhang
Xiaoqin Tong
Weiming Lou
Lulu Le
Xiaoli Tang
Fen Fu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2018
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-018-0467-z

Other articles of this Issue 1/2018

Journal of Ovarian Research 1/2018 Go to the issue