Proteomic analysis of ovarian carcinoma reveals diagnostic and prognostic biomarkers with histotype- and stage-specificity.

Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer, due to asymptomatic early stages, vague symptoms in later stages, and limited clinical tools. Despite distinct clinicopathologic features, all EOC histotypes typically receive identical primary treatment, and are often studied as a single entity. We analyzed the proteome of 244 patients and identified differentially abundant proteins (DAPs) with and without stage specificity across histotypes and constructed panels of DAPs to distinguish histotypes in both early and late stages. Survival analysis was performed to find proteins associated with clinical outcomes, and enrichment analysis was conducted to reveal biological processes connected to prognosis and the proteins involved. Here we find DAPs without (e.g. S100A1, AGR2, CTH) and with (TSPYL, VWA2, GPC6, S100P) stage-specificity for each histotype. Survival analysis revealed histotype- and stage-specific prognostic markers (e.g., EXO3CL2, PPIL6, GYG1, GAPDH), while biological process enrichment highlighted pathways underlying clinical outcomes. Our findings provide novel diagnostic and prognostic biomarker candidates and insights into mechanisms driving EOC progression with histotype- and stage-specificity. This may aid the development of improved clinical tools for detection, patient stratification, and targeted therapies in EOC.