Identification of Candidate Biomarkers Associated with Ovarian Cancer Progression and Prognosis by Integrated Microarray Analysis

Abstract Ovarian cancer (OC) is one of the most common gynecological malignancies, with high mortality and few prognostic biomarkers. This study aimed to identify differentially expressed genes (DEGs) relevant to the prognosis of ovarian cancer. First, we performed differential analysis on GSE38666, GSE14407, GSE27651 and GSE18520 expression profile datasets from the Gene Expression Omnibus (GEO) database and obtained 638 DEGs using a Venn diagram tool. Second, we constructed a protein–protein interaction (PPI) network with the STRING database and used the Molecular Complex Detection (MCODE) plugin in Cytoscape software to perform gene cluster analyses for 269 upregulated and 367 downregulated DEGs, respectively. Based on the results of gene cluster analyses, we selected two gene clusters of upregulated DEGs with network scores of > 10 and two gene clusters of downregulated DEGs with scores of > 5 for further functional analysis with the clusterProfiler package. In addition, we analyzed the effect of genes from those clusters on the overall survival (OS) and progression-free survival (PFS) of OC patients based on Kaplan–Meier Plotter and PrognoScan databases. The gene clusters of upregulated DEGs are involved mainly in cell division and cell proliferation, and the genes of downregulated DEGs primarily participate in the TGF-β signaling pathway and various metabolic processes. Via cross-validation of survival analysis, we identified four hub genes (AURKA, CDCA5, CEP55 and UBE2C) that correlated with ovarian cancer OS and PFS, which derived from the upregulated DEGs. Patients with these four hub genes trended toward worse OS and PFS than patients with low expression. Unfortunately, no significantly prognosis-related genes were detected among downregulated clusters. The mRNA expression of these four genes were analysed using the Oncomine and GEPIA databases, and the result revealed that the mRNA expression of AURKA,CDCA5,CEP55 and UBE2C was greatly upregulated in OC tissues compare with normal tissues. The gene set/pathway primarily showed alterations in amplification and deep deletion, and correlation analysis indicated significant positive correlations between AURKA, CDCA5, CEP55 and UBE2C. Nevertheless, for clarifying the protein expression levels of the four prognostic genes, the staining of the immunohistochemistry (IHC) were obtained base on the Human Protein Atlas, and was showed the proteins levels of these four genes was significantly elevated in patients with OC. Our results revealed that these four hub genes may mediate ovarian cancer development and have valuable clinical potential as prognostic biomarkers for OC patients.