Proteomics and Bioinformatics Investigations Link Overexpression of FGF8 and Associated Hub Genes to the Progression of Ovarian Cancer and Poor Prognosis

Abstract

Ovarian cancer’s asymptomatic nature, high recurrence rate, and resistance to platinum-based chemotherapy highlight the need to find and characterize new diagnostic and therapeutic targets. While prior studies have linked aberrant expression of fibroblast growth factor 8 (FGF8) to various cancer types, its precise role has remained elusive. Recently, we observed that FGF8 silencing reduces the cancer-promoting properties of ovarian cancer cells, and thus, this study aimed to understand how FGF8 regulates the development of ovarian cancer. LC-MS/MS-based quantitative proteomics analysis identified 418 DEPs, and most of them were downregulated in FGF8-silenced ovarian cancer cells. Many of these DEPs are associated with cancer progression and unfavorable prognosis. To decipher the biological significance of DEPs, bioinformatics analyses encompassing gene ontology, pathway analysis, protein-protein interaction networks, and expression analysis of hub genes were carried out. Hub genes identified in the FGF8 protein network were upregulated in ovarian cancer compared to controls and were linked to poor prognosis. Subsequently, the expression of hub genes was correlated with patient survival and regulation of the tumor microenvironment. Conclusively, FGF8 and associated hub genes help in the progression of ovarian cancer, and their overexpression may lead to higher immune infiltration, poor prognosis, and poor survival.