Ovarian cancer proteomic landscape changes across different pathological stages and biomarker-sets identified with integrative multiomics analysis

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Background Ovarian cancer (OV) is a highly lethal gynecological malignant tumor, with a high mortality, low survival rate, and lacking effective biomarkers. The concept of predictive, preventive, and personalized medicine (PPPM) underscores the need for early warning systems and tailored interventions, creating a demand for reliable, stage-specific biomarkers. Methods A comprehensive proteomic analysis of 60 OV tissues across pathological stages I-IV, and 17 benign ovarian tissues were analyzed with data-independent acquisition (DIA) mass spectrometry. Moreover, these proteomic findings were integrated with TCGA/GTEx data for survival analysis and key molecules, followed by experimental validation with western blot and multiplex immunohistochemistry. Results Totally, 1,669 differentially abundant proteins (DAPs) were significantly different in each pathological stage (I, II, III, and IV) of OVs compared to controls. DAPs in the early stage (Stage I-II) were mainly enriched in biological processes related to cell proliferation, such as cell cycle process and chromosome segregation, DAPs in advanced stages (Stages III–IV) were mainly enriched in pathways including extracellular matrix (ECM) organization and cell adhesion. Trend cluster analysis of these DAPs identified six types of trend clusters across different stages of OVs (C1–C6). PPI network analysis identified 28 hub proteins with multiple centrality algorithms. Of them, hub protein SMC2 was localized at nuclear and upregulated during early stage (I/II), which was significantly upregulated at its mRNA and protein levels in OV tissues with TCGA/GTEx, western blotting, and multiplex immunofluorescence analyses, and had a significant relationship with reduced overall survival (HR = 1.31, 95% CI: 1.12–1.55, p = 0.0011) with Kaplan-Meier survival analysis. Conclusion This study provided the large-scale stage-resolved proteomic atlas of OVs, identifies a 28-protein core module governing cell cycle and genome stability, and reveals SMC2 plays crucial roles in OVs.

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