Meta-analysis Of MRNA Expression Profiles To Identify Key Genes And Pathways In Proliferative High-grade Serous Ovarian Cancer

Objectives:Based on the gene expression profile of ovarian cancer,through the high-grade serous ovarian cancer(HGS-OvCa)classifier,we obtain different subtypes of HGS-OvCa.The key genes and pathways of Proliferative high-grade serous ovarian cancer were identified.Methods:We conducted a comprehensive search of the GEO database to select the data set that meets the inclusion criteria.Based on the findings of the TCGA team and Tothill and others on ovarian cancer subtypes,we established a cross-platform HGS-OvCa subtype classifier,So that we can get four different subtypes of HGS-OvCa,namely differentiated type,immune type,Proliferative type and interstitial type.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:Five gene expression profiles(GSE6008,GSE18520,GSE26712,GSE27651 and GSE9891)were finally included.By comparing proliferative high-grade serous ovarian cancer and non-proliferative HGS-OvCa,a total of 622 differentially expressed genes,229 up regulated genes and 433 down regulated genes were identified in this study.The enrichment analysis of go and KEGG pathways showed that up-regulated genes were significantly enriched in cell division,cell cycle,ATP binding and adenine nucleotide binding.The down-regulated genes are involved in cell proliferation,cell movement,cancer pathways,cell membrane synthesis,and protein complex binding.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 >68 were selected from PPI network,and the Kaplan-Meier analysis of TOP2 A,CDH1,VEGFA,EZH2 and CCNB1 suggested that they were related to the prognosis of the disease.Conclusions:Established a cross-platform HGS-OvCa data classification model through TCGA databases.By comparing proliferative high-grade serous ovarian cancer and non-proliferative HGS-OvCa,a total of 622 differentially expressed genes,229 up regulated genes and 433 down regulated genes were identified in this study.Among them,TOP2 A,CDH1,VEGFA,EZH2 and CCNB1 as the key genes that might become potential targets for future research the molecular mechanisms and biomarkers of proliferative ovarian cancer.