Identification of prognosis-related hub genes of ovarian cancer through bioinformatics analyses and experimental verification.

Abstract

Ovarian cancer (OC) is a lethal and highly prevalent disease in women worldwide. The disease is often diagnosed in late stages, which leads to its rapid progression and low survival rate. This study aims to identify new prognostic genes for OC. Based on 2 datasets from the National Center for Biotechnology Information Gene Expression Omnibus public database, we constructed 2 Weighted Gene Co-expression Network Analysis networks. Then, we selected and intersected 2 key modules to screen key genes. Enrichment analyses were performed, and a protein-protein interaction network was constructed. The cytoHubba plugin of Cytoscape and survival analysis were used to screen hub genes related to prognosis. The expression of hub genes was analyzed by GEPIA and verified by quantitative Real-Time PCR. Gene alteration frequency analysis, gene set variation analysis, immune infiltration analysis, drug sensitivity analysis, tumor mutation burden, and neoantigen analyses were conducted to determine the prognostic value and molecular mechanisms of the hub genes. In total, 214 key genes were selected from 2 Weighted Gene Co-expression Network Analysis networks, and 3 hub genes, namely ALDH1A2, CLDN4, and GPR37, were identified as prognostic candidates through cytoHubba and survival analysis. Three hub genes were significantly associated with overall survival of OC patients. GEPIA and quantitative Real-Time PCR indicated that ALDH1A2 expression was significantly downregulated, while expression of CLDN4 and GPR37 was upregulated in OC samples compared with normal samples. CIBERSORT showed that 3 hub genes were closely associated with the infiltrating immune cells. GDSC showed that hub genes expression influenced IC50 values of chemotherapeutic drugs. OC patients with high expression of ALDH1A2 and CLDN4 had lower TMB and low ALDH1A2 expression could produce a larger number of neoantigens. In conclusion, the 3 hub genes (ALDH1A2, CLDN4 and GPR37) identified through bioinformatics analyses in the present study may serve as OC prognosis biomarkers. The study findings offer valuable insights into OC progression and mechanisms.