Claudin-4 Overexpression Predicts Poor Survival and Platinum Resistance in Epithelial Ovarian Cancer: A Potential...

Background/Objectives: Epithelial ovarian cancer (EOC) is a leading cause of death among forms of gynecologic cancer. Significant causes of mortality include high recurrence rates and the development of resistance to platinum-based chemotherapy. This highlights the need for reliable prognostic biomarkers to improve patient stratification and inform treatment decisions. Claudin-4, a tight junction protein frequently overexpressed in epithelial tumors, has been associated with tumor progression and resistance to chemotherapy. Methods: We retrospectively analyzed 83 patients with EOC who underwent debulking surgery. Claudin-4 expression was assessed by immunohistochemistry and categorized as high or low based on a semi-quantitative scoring system. Survival outcomes were evaluated using Kaplan-Meier analysis and Cox regression. Predictors of platinum resistance were examined using logistic regression. Results: High Claudin-4 expression was observed in 55.4% of cases and was associated with significantly shorter disease-free survival (DFS) (23 vs. 66 months, p = 0.00024) and overall survival (OS) (85 months vs. NR, p = 0.0031). In multivariable analysis, platinum resistance (DFS; HR 4.99, OS; HR 4.27) and high Claudin-4 expression (DFS; HR 2.46, OS; HR 3.59) were independent predictors of poor outcomes. Logistic regression further demonstrated that high Claudin-4 expression and interval debulking surgery were independent predictors of platinum resistance. Conclusions: High Claudin-4 expression was associated with inferior survival and an increased risk of platinum resistance in EOC. Our findings suggest that Claudin-4 may serve as a negative prognostic biomarker and a potential therapeutic target. Future prospective studies are warranted to further elucidate the underlying mechanisms and validate Claudin-4's clinical utility.