AUTHOR=Yasar Seyma , Melekoglu Rauf 

TITLE=Proteomic alterations in ovarian cancer—Predicting residual disease status using artificial intelligence and SHAP-based biomarker interpretation

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1562558

DOI=10.3389/fmed.2025.1562558

ISSN=2296-858X

ABSTRACT=IntroductionHigh-grade serous ovarian cancer (HGSOC) is the most aggressive and prevalent subtype of ovarian Treatment outcomes are significantly influenced by residual disease status following neoadjuvant chemotherapy (NACT). Predicting residual disease before surgery can improve patient stratification and personalized treatment strategies.MethodsThis study analyzed pre-NACT proteomic data from 20 HGSOC patients treated with NACT. Patients were categorized into two groups based on surgical outcomes: no residual disease (R0, n = 14) and suboptimal residual disease (R1, n = 6). From an initial set of 97 differentially expressed proteins, 18 significant proteins were selected using the BORUTA feature selection method. Three machine learning models-Random Forest (RF), Support Vector Machine (SVM), and Bootstrap Aggregation with Classification and Regression Trees (BaggedCART)-were developed and evaluated.ResultsThe Random Forest model achieved the best performance with an AUC of 0.955, accuracy of 0.830, sensitivity of 0.904, specificity of 0.763, and F1-score of 0.839. SHapley Additive exPlanations (SHAP) analysis identified five proteins (P48637, O43491, O95302, Q96CX2, and P49189) as the most influential predictors of residual disease. These proteins, including glutathione synthetase and peptidyl-prolyl cis-trans isomerase FKBP9, are associated with chemotherapy resistance mechanisms.DiscussionThe findings demonstrate the potential of integrating proteomic data with machine learning techniques for predicting surgical outcomes in HGSOC. Identified protein signatures may serve as valuable biomarkers for anticipating NACT response and informing clinical decision-making, ultimately contributing to personalized patient care.