Serum Fibroblast Growth Factor 7 Provides Complementary Diagnostic and Prognostic Value to CA125 and HE4 in Ovarian Cancer

Abstract

Background: Early detection and risk stratification in ovarian cancer (OC) remain challenging, particularly in patients with low levels of conventional serum markers. This study primarily evaluated serum fibroblast growth factor 7 (FGF7) as a complementary biomarker to CA125 and HE4 for the diagnosis of OC, and secondarily explored its association with prognosis. Methods: A total of 620 participants were included (312 OC, 168 benign ovarian tumors, and 140 healthy controls). Serum FGF7, CA125, and HE4 levels were measured, and a three-marker diagnostic model (FGF7 + CA125 + HE4) was developed and evaluated using an internal split-sample validation framework. Diagnostic performance was assessed using receiver operating characteristic analysis, including clinically relevant subgroups such as early-stage OC and patients with low CA125 or HE4 levels. Overall survival was analyzed using Kaplan–Meier methods and Cox regression, and incremental value was further examined using reclassification and decision-curve analyses. Results: Serum FGF7 showed a stepwise increase from healthy controls to benign tumors and OC (median, 19.62 vs 24.85 vs 42.37 pg/mL; P < 0.001). In the training cohort, FGF7 alone showed moderate discrimination (AUC, 0.76), whereas the three-marker model outperformed the CA125 + HE4 model (AUC, 0.97 vs 0.95; sensitivity, 92.11% vs 90.44%; specificity, 92.09% vs 89.53%). In the internal validation cohort, the three-marker model maintained robust performance (AUC, 0.95 vs 0.93; P = 0.032), with greater incremental benefit in early-stage OC (AUC, 0.90 vs 0.86; P = 0.041), low-CA125 disease (0.88 vs 0.82; P = 0.028), and low-HE4 disease (0.89 vs 0.84; P = 0.034). During a median follow-up of 42.67 months, high FGF7 independently predicted worse survival (HR, 1.92; 95% CI, 1.31–2.82), and concurrent elevation of all three biomarkers further stratified prognosis (HR, 2.41; 95% CI, 1.60–3.62). Conclusions: Serum FGF7 may provide complementary diagnostic value in OC, particularly when combined with CA125 and HE4. Its added value was most evident in early-stage disease and in patients with low levels of conventional biomarkers. Elevated FGF7 was also associated with poorer survival, suggesting possible additional value in risk stratification.