Identifying Genes As Potential Prognostic Indicators In Patients With Serous Ovarian Cancer Resistant To Carboplatin Using Integrated Bioinformatics Analysis

Background: Serous ovarian cancer(SOC)accounts for more than 50% of all epithelial ovarian cancers.However,patients with SOC present with various degrees of response to platinum-based chemotherapy and thus have different survival.Objective: This study aimed to identify the candidate genes in carcinogenesis and drug resistance of SOC by analyzing the microarray datasets GDS1381 and GDS3592.Materials and methods: GDS1381 and GDS3592 were downloaded from the Gene Expression Omnibus database.A total of 219 differentially expressed genes(DEGs)were identified.Potential genes,which might indicate a response to carboplatin and thus the prognosis of SOC,were analyzed.Results: The enriched functions and pathways of DEGs included extracellular region,extracellular space,extracellular exosome,and so forth.On screening the upregulated and downregulated genes on the Connectivity MAP,10 small-molecule drugs were identified that might be helpful in improving drug sensitivity in patients with ovarian cancer.Thirty hub genes were screened for further analysis after constructing the protein–protein interaction network.Through survival analysis,comparison of genes across numerous analyses,and immunohistochemistry,GNAI1,nonstructural maintenance of chromosomes(non-SMC)condensin I complex subunit H(NCAPH),matrix metallopeptidase 9(MMP9),aurora kinase A(AURKA),and enhancer of zeste 2 polycomb repressive complex 2 subunit(EZH2)were identified as the key molecules that might be involved in the carcinogenesis and carboplatin resistance of SOC.Conclusion: GNAI1,NCAPH,MMP9,AURKA,and EZH2 should be testified in further studies for the likelihood of their participation in the carcinogenesis and carboplatin response of SOC.Objective: To study the expression of MAF1 in ovarian cancer and its effect on the prognosis of ovarian cancer.Methods: Immunohistochemistry was used to identify the expression of MAF1 in ovarian serous carcinoma tissues(n=87)compared with that of normal ovarian tissues(n=6).Clinical characters of each samples were analyzed for their correlation with expression of MAF1.Bioinformatics analysis was used to identify the influence of MAF1 expression on the survival rate in patients with ovarian cancer and the co-expression genes with MAF1 and their enriched pathways.Results: Expression of MAF1 in ovarian cancer tissues was higher than normal ovarian tissues.The results demonstrated the association of MAF1 expression with different FIGO stage(P=0.009),vital status(p = 0.015),platinum resistance(p=0.002).However,there are no correlations among age of onset,lymph node metastasis,peritoneal metastasis,distant recurrence,differentiation grade,ascites seeing tumor cells(+),CA19-9,CEA,CA125 and HE4 levels with expression of MAF1.Meanwhile,higher expression of MAF1 indicated a poor prognostic in patients with ovarian cancer.Further analysis using online database supported this survival result.Moreover,MAF1 and its Co-expressed genes are mostly enriched in theglucose metabolism pathway.Conclusion: MAF1 expression is up-regulated in patients with OSC and high expression of MAF1 might have effects on platinum resistance and survival of patients with OSC.