Meta-Analysis Of MRNA Expression Profiles To Identify Key Genes And Pathways In Ovarian Cancer

Objectives:To identify the key genes and pathways of ovarian cancer by comparing gene expression profiles of ovarian cancer tissues with normal ovarian tissues.Methods:We performed a comprehensive search of Gene Expression Omnibus(GEO)database and selected datasets that met the inclusion criteria.We identified differentially expressed genes(DEGs)by a meta-analysis that based on expression profiling microarrays and performed GO and KEGG pathway enrichment analysis for the most significant DEGs.The significant gene modules were identified from protein-protein interaction(PPI)network of DEGs applying MCODE software and GO and KEGG pathway enrichment analysis for the DEGs of each module were performed.Moreover,the hub genes were screened using CentiScaPe 2.1 software.The Kaplan Meier plotter(KM plotter,http://kmplot.com/analysis/)was used to assess the effect of the hub genes on survival.Results:Seven gene expression profiles(GSE6008,GSE18520,GSE26712,GSE27651,GSE29450,GSE36668 and GSE52037)containing 396 ovarian cancer samples and54 normal control samples were included.Compared with normal ovarian tissue,a total of 245 upregulated genes and 318 downregulated genes were identified in our study.Enrichment analysis of the GO function and KEGG pathway showed that upregulated genes were significantly enriched in cell division,cell cycle,tight junction,oocyte meiosis,while downregulated genes were associated with response to endogenous stimulus,complement and coagulation cascades,cGMP-PKG signaling pathway,serotonergic synapse.Four significant gene modules were identified from protein-protein interaction(PPI)network of differentially expressed genes applying MCODE software.Moreover,seven hub genes with degree >45 wereselected from PPI network,and the Kaplan-Meier analysis of TOP2 A,CDK1,VEGFA,and CCNB2 suggested that they were related to the prognosis of the disease.Module analysis showed that the five hub genes including TOP2 A,CDK1,BIRC5,CCNB2,and TYMS belonged to module 1.Conclusions:Compared with normal ovarian tissue,we identified a total of 563 differentially expressed genes and seven hub genes.Among them,TOP2 A,CDK1,and CCNB2 as the key genes that might become potential targets for future research the molecular mechanisms and biomarkers of ovarian cancer.At the same time,we suggested that the cell cycle pathway might be a key pathway for pathogenesis of ovarian cancer.