Integrative Multi-Omics Analysis Reveals Molecular Signatures of Recurrence in Paired Primary and Recurrent High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive form of epithelial ovarian cancer, characterized by high recurrence rates and poor clinical outcomes. In this study, we identify molecular signatures associated with recurrence by conducting integrative transcriptomic and proteomic analyses on paired primary and recurrent HGSOC tissues from 34 patients. RNA sequencing and proteomic profiling revealed 185 differentially expressed genes (DEGs) and 36 differentially expressed proteins (DEPs) linked to recurrence. Pathway Enrichment and Ingenuity Pathway Analysis highlighted the involvement of immune cell trafficking, cell signaling, and MAPK pathway activation in recurrent tumors. Survival analysis identified seven DEGs significantly correlated with recurrence-free survival; among these, IL7R, IRF8, and PTPRC were upregulated in recurrent tumors and associated with poor prognosis, while NSG1 was downregulated and linked to favorable outcomes. Immunohistochemistry validated the differential expression of these markers at the protein level. Proteomic analysis demonstrated that recurrent tumor-specific DEGs are functionally linked to MAPK signaling. Co-expression analyses revealed dynamic regulatory interactions between DEGs and DEPs, suggesting context-dependent molecular shifts during recurrence. This integrative multi-omics approach reveals key molecular alterations underlying HGSOC recurrence and identifies IL7R, IRF8, PTPRC, and NSG1 as potential prognostic biomarkers and therapeutic targets. Our findings provide a foundation for targeted strategies to improve outcomes for patients with recurrent HGSOC.