Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2021 Jun 18

PMID 34143800

Citations 8

Authors

Ting Gui

Chenhe Yao

Binghan Jia

Keng Shen

Affiliations

Soon will be listed here.

Abstract

Background: Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets is of great value.

Methods: Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and were subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed based on the STRING database. The expression of hub genes was validated in GEPIA and GEO. The relationship of hub genes expression with tumor stage and overall survival and progression-free survival of EOC patients was investigated using the cancer genome atlas data.

Results: A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through PPI network analysis, the top 20 genes were screened out, among which 4 hub genes, which were not researched in depth so far, were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues compared with normal tissues, but their expression decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival statistically.

Conclusion: Two hub genes, CDCA5 and ESPL1, identified as probably playing tumor-promotive roles, have great potential to be utilized as novel therapeutic targets for EOC treatment.

Citing Articles

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Zhang W, Liang Z, He R, Huang Z, Wang X, Wei M Heliyon. 2024; 10(10):e31192.

PMID: 38813236 PMC: 11133711. DOI: 10.1016/j.heliyon.2024.e31192.

CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.

Liu Y, Han T, Xu Z, Wu J, Zhou J, Guo J J Transl Med. 2024; 22(1):335.

PMID: 38589907 PMC: 11000299. DOI: 10.1186/s12967-024-05038-5.

PAX2 mediated upregulation of ESPL1 contributes to cisplatin resistance in bladder cancer through activating the JAK2/STAT3 pathway.

Zhang W, Wang Y, Tang Q, Li Z, Sun J, Zhao Z Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(9):6889-6901.

PMID: 38573552 DOI: 10.1007/s00210-024-03061-3.

CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells.

Zhang Q, Zhang R, Li Y, Yang X J Ovarian Res. 2024; 17(1):68.

PMID: 38539247 PMC: 10967103. DOI: 10.1186/s13048-024-01393-5.

CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications.

Kim N, Kim M, Pyo J, Lee S, Jang J, Lee D Biomedicines. 2023; 11(11).

PMID: 38001911 PMC: 10669377. DOI: 10.3390/biomedicines11112910.

References

Feng H, Gu Z, Li Q, Liu Q, Yang X, Zhang J . Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis. J Ovarian Res. 2019; 12(1):35. PMC: 6477749. DOI: 10.1186/s13048-019-0508-2. View

Finetti P, Guille A, Adelaide J, Birnbaum D, Chaffanet M, Bertucci F . ESPL1 is a candidate oncogene of luminal B breast cancers. Breast Cancer Res Treat. 2014; 147(1):51-9. DOI: 10.1007/s10549-014-3070-z. View

Magdalou I, Lopez B, Pasero P, Lambert S . The causes of replication stress and their consequences on genome stability and cell fate. Semin Cell Dev Biol. 2014; 30:154-64. DOI: 10.1016/j.semcdb.2014.04.035. View

Li G, Han L, Ren F, Zhang R, Qin G . Prognostic value of the tumor-specific ceRNA network in epithelial ovarian cancer. J Cell Physiol. 2019; 234(12):22071-22081. DOI: 10.1002/jcp.28770. View

Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D . Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003; 13(11):2498-504. PMC: 403769. DOI: 10.1101/gr.1239303. View

Zhao L, Li Y, Zhang Z, Zou J, Li J, Wei R . Meta-analysis based gene expression profiling reveals functional genes in ovarian cancer. Biosci Rep. 2020; 40(11). PMC: 7677829. DOI: 10.1042/BSR20202911. View

Qadir F, Lalli A, Dar H, Hwang S, AlDehlawi H, Ma H . Clinical correlation of opposing molecular signatures in head and neck squamous cell carcinoma. BMC Cancer. 2019; 19(1):830. PMC: 6708230. DOI: 10.1186/s12885-019-6059-5. View

Zhang J, Zhu W, Wang Q, Gu J, Huang L, Sun X . Differential regulatory network-based quantification and prioritization of key genes underlying cancer drug resistance based on time-course RNA-seq data. PLoS Comput Biol. 2019; 15(11):e1007435. PMC: 6827891. DOI: 10.1371/journal.pcbi.1007435. View

Xu J, Zhu C, Yu Y, Wu W, Cao J, Li Z . Systematic cancer-testis gene expression analysis identified CDCA5 as a potential therapeutic target in esophageal squamous cell carcinoma. EBioMedicine. 2019; 46:54-65. PMC: 6710982. DOI: 10.1016/j.ebiom.2019.07.030. View

10.

Fan X, Shi L, Fang H, Cheng Y, Perkins R, Tong W . DNA microarrays are predictive of cancer prognosis: a re-evaluation. Clin Cancer Res. 2010; 16(2):629-36. DOI: 10.1158/1078-0432.CCR-09-1815. View

11.

Tercero J, Labib K, Diffley J . DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p. EMBO J. 2000; 19(9):2082-93. PMC: 305696. DOI: 10.1093/emboj/19.9.2082. View

12.

Tian Y, Wu J, Chagas C, Du Y, Lyu H, He Y . CDCA5 overexpression is an Indicator of poor prognosis in patients with hepatocellular carcinoma (HCC). BMC Cancer. 2018; 18(1):1187. PMC: 6267780. DOI: 10.1186/s12885-018-5072-4. View

13.

Liu L, Lin J, He H . Identification of Potential Crucial Genes Associated With the Pathogenesis and Prognosis of Endometrial Cancer. Front Genet. 2019; 10:373. PMC: 6499025. DOI: 10.3389/fgene.2019.00373. View

14.

Gao J, Sai N, Wang C, Sheng X, Shao Q, Zhou C . Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo. Tumour Biol. 2010; 32(1):53-61. DOI: 10.1007/s13277-010-0090-0. View

15.

Wei J, Yin Y, Deng Q, Zhou J, Wang Y, Yin G . Integrative Analysis of MicroRNA and Gene Interactions for Revealing Candidate Signatures in Prostate Cancer. Front Genet. 2020; 11:176. PMC: 7057858. DOI: 10.3389/fgene.2020.00176. View

16.

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. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

17.

Bai L, Ren Y, Cui T . Overexpression of , , , and Coregulated Cell Cycle and Promoted Hepatocellular Carcinoma Development. J Comput Biol. 2019; 27(6):965-974. DOI: 10.1089/cmb.2019.0254. View

18.

Subramanyam S, Jones W, Spies M, Spies M . Contributions of the RAD51 N-terminal domain to BRCA2-RAD51 interaction. Nucleic Acids Res. 2013; 41(19):9020-32. PMC: 3799448. DOI: 10.1093/nar/gkt691. View

19.

Wu Q, Zhang B, Sun Y, Xu R, Hu X, Ren S . Identification of novel biomarkers and candidate small molecule drugs in non-small-cell lung cancer by integrated microarray analysis. Onco Targets Ther. 2019; 12:3545-3563. PMC: 6526173. DOI: 10.2147/OTT.S198621. View

20.

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B . STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003; 31(1):258-61. PMC: 165481. DOI: 10.1093/nar/gkg034. View