Circulating GDF-15: an intriguing candidate biomarker for the differential diagnosis of ovarian masses

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological malignancies. Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine, has emerged as a potential biomarker in several cancers. However, its biological and diagnostic significance in ovarian pathology remains poorly defined. This retrospective, single-centre, proof-of-concept study aimed to evaluate circulating GDF-15 levels in EOC and benign ovarian cysts (BOC). A total of 48 women with histologically confirmed EOC and 40 patients with BOC were included. Circulating GDF-15 levels were assessed by ELISA and Western blot (WB) analysis. Circulating GDF-15 levels were significantly higher in EOC patients compared with BOC. Receiver operating characteristic (ROC) analysis identified an optimal diagnostic threshold of 1020 pg/mL, yielding an Area Under the Curve (AUC) of 0.924 (95% CI: 0.863-0.984) with 93.8% sensitivity and 82.5% specificity (optimism-corrected via bootstrap resampling: 91.2% sensitivity and 80.5% specificity p < 0.0001). Vimentin, was evaluated by WB in serum samples and by immunofluorescence in tumour tissue sections. Vimentin expression was predominantly detected in sera from EOC patients. Immunofluorescence analysis of tumour tissue showed distinct populations of GDF-15-positive and vimentin-positive cells without direct structural colocalization. In conclusion, GDF-15 shows promise as a complementary biomarker within multi-marker panels, assisting with diagnosis in challenging scenarios such as indeterminate adnexal masses and gray zones with borderline or discordant results from conventional markers.