Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer

Abstract

Objectives There is a need for identification of new biomarkers improving our understanding, diagnosis, and follow-up of ovarian cancer. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily, and GDF-15 overexpression has been found in several cancer forms but has not been explored in ovarian cancer. The aim of the study was to explore preoperative plasma concentration and tissue expression of growth differentiation factor (GDF)-15 in ovarian tumors. Methods GDF-15 concentration was measured by immunoradiometric assay in plasma samples from patients with invasive ovarian cancer ( n = 125), borderline ovarian tumor (BOT, n = 43), and benign ovarian tumor ( n = 144), from healthy women ( n = 40), as well as in effusion samples ( n = 44) from women with advanced ovarian cancer. Sections of ovarian carcinoma ( n = 20), BOT ( n = 9), and cystadenoma ( n = 7) were immunostained for GDF-15. Results Median plasma GDF-15 concentration was elevated in ovarian cancer as compared to healthy controls and women with benign ovarian tumors or BOT ( p < 0.001). GDF-15 plasma concentration correlated inversely with survival time and was an independent predictor of survival, after correction for FIGO stage and age ( p = 0.01). GDF-15 protein was cytoplasmatically expressed in serous tumor cells and detectable in high concentrations in effusion samples. Conclusion GDF-15 emerges as a new potential biomarker in ovarian cancer.