The OvarianTag™ Biomarker Panel Emerges as a Prognostic Tool to Guide Clinical Decisions in Cisplatin-Based Treatment of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, often diagnosed at an advanced stage due to its asymptomatic progression. The high recurrence rate and development of platinum-based chemotherapy resistance contribute to its poor prognosis. Despite advancements in molecular profiling, predictive biomarkers for chemotherapy response and recurrence risk remain limited. In this study, we developed OvarianTag™, a biomarker panel integrating apoptosis and necroptosis pathways, to predict chemotherapy benefit and disease progression in EOC patients. This observational study was conducted in two phases. In the first phase, 45 patients were recruited, and RNA was extracted from fresh ovarian tissues (normal, benign, and malignant). qRT-PCR was performed to assess the relative expression of genes involved in apoptosis and necroptosis-regulated cell death pathways. Machine learning algorithms were applied to identify the relevant prognostic markers, leading to the development of OvarianTag™. In the second phase, 55 additional EOC patients were included, and their formalin-fixed, paraffin-embedded (FFPE) tumor samples were analyzed using qRT-PCR. The classifier algorithm incorporated hierarchical clustering to stratify patients based on gene expression profiles. Significant differences in <i>TNFRSF10C/TRAIL-R3</i>, <i>TNFRSF10B/TRAIL-R2</i>, and <i>CASP8</i> expression levels were observed between patient groups. <i>CASP8</i> downregulation was strongly correlated with platinum resistance and a poor prognosis. Decision tree models achieved 83.3% accuracy in predicting platinum response and 79.2% accuracy in recurrence risk stratification. The OvarianTag™ classifier demonstrated high sensitivity and specificity in identifying high-risk patients, supporting its potential as a prognostic tool. The OvarianTag™ panel provides a novel approach for risk stratification in EOC, integrating apoptosis and necroptosis pathways to refine chemotherapy response prediction and recurrence risk assessment. This molecular assay has the potential to guide personalized treatment strategies, enhancing clinical decision-making and improving patient outcomes. Further validation in independent cohorts is warranted to establish its clinical utility.