Diagnostic and prognostic values of circulating growth differentiation factor-15 and osteopontin in uterine sarcoma

Uterine sarcoma is an aggressive malignancy that is difficult to distinguish from benign leiomyomas pre-operatively. This study aimed to identify circulating biomarkers to improve differential diagnosis and prognostication. The serum and tissue levels of growth differentiation factor-15 (GDF15), progranulin (PGN), and osteopontin (OPN) were measured in patients with uterine sarcoma (n = 38) and leiomyoma (n = 67). The levels were correlated with diagnosis and patient survival. The serum and tissue levels of GDF15 and OPN were significantly higher in uterine sarcomas than in leiomyomas (p < 0.001). High GDF15 levels were associated with significantly poorer progression-free survival (PFS) (p < 0.001). In a multivariate analysis including established markers cancer antigen 125 (CA125) and lactate dehydrogenase (LDH), only GDF15 remained an independent predictor of PFS [hazard ratio (HR) 3.01, 95% confidence interval (CI) 1.04-8.67, p = 0.042]. The prognostic power of GDF15 was confirmed by an analysis that excluded carcinosarcomas. GDF15 and OPN are promising biomarkers for pre-operatively differentiation of uterine sarcoma from leiomyoma. Furthermore, GDF15 is a strong, independent prognostic factor for PFS in patients with uterine sarcoma and has the potential to improve diagnostic accuracy and clinical management.