Longitudinal Plasma Proteomic Remodeling in Ovarian Cancer

This longitudinal observational study investigates treatment-associated changes in the circulating plasma proteome of patients with ovarian cancer undergoing standard treatment. Although CA125 and HE4 are established biomarkers for monitoring treatment response, they provide only a limited view of the complex biological processes occurring during therapy. The study includes patients with epithelial ovarian cancer and primary peritoneal Müllerian tumors who underwent surgery and/or platinum-based chemotherapy. Plasma samples were collected at three predefined treatment timepoints: before surgery (T1), after surgery (T2), and after completion of chemotherapy (T3). A panel of 92 circulating proteins was quantified using Olink proximity extension assay technology. Longitudinal proteomic changes were evaluated in relation to established clinical biomarkers (CA125 and HE4), exploratory proliferation-associated biomarker thymidine kinase 1 (TK1), and KELIM-defined chemosensitivity. The primary objective is to characterize treatment-associated remodeling of the circulating proteome and determine whether these molecular changes reflect tumor burden reduction, treatment exposure, or chemotherapy sensitivity. Secondary objectives include identification of proteins and biological pathways associated with treatment timepoints and assessment of concordance between proteomic changes and established clinical biomarkers. This study aims to improve understanding of dynamic tumor-host interactions during ovarian cancer treatment and to explore the potential role of longitudinal proteomic profiling as a complement to conventional biomarker monitoring.

Inclusion Criteria: * Age ≥18 years. * Histologically confirmed epithelial ovarian cancer or primary peritoneal Müllerian carcinoma. * Undergoing standard treatment including surgery and/or systemic therapy. * Availability of plasma samples collected at one or more predefined treatment timepoints (pre-operative, post-operative, and/or post-chemotherapy). * Availability of corresponding clinical and biomarker data (CA125 and/or HE4). * Written informed consent Exclusion Criteria * Non-epithelial ovarian malignancies. * Insufficient plasma sample volume or inadequate sample quality for proteomic analysis. * Missing essential clinical data required for study analyses. * Withdrawal of informed consent. * Concurrent participation in another study that would prevent interpretation of biomarker analyses.