NEDD9 overexpression is associated with the progression of and an unfavorable prognosis in epithelial ovarian cancer

Abstract

Neural precursor cell-expressed, developmentally down-regulated 9 (NEDD9), a scaffolding protein, has been identified as a prometastatic and poor prognostic gene in multiple malignant tumors. However, the potential role of the NEDD9 protein in epithelial ovarian cancer (EOC) remains unclear. In the present study, we investigated the expression of NEDD9 and the correlation between NEDD9 expression and prognosis in EOC. NEDD9 expression was detected in 129 archived EOC specimens by immunohistochemical staining and in 28 freshly frozen EOC specimens by Western blotting. The expression of NEDD9 was evaluated in ovarian cancer cell lines by Western blotting and immunofluorescence. The association between the expression of NEDD9 and prognosis was determined by survival analysis. Results suggested that NEDD9 was overexpressed in EOC specimens compared with noninvasive epithelial ovarian tumors and normal ovarian specimens. A high level of NEDD9 expression significantly correlated with advanced-stage tumors (International Federation of Gynecology and Obstetrics classes III-IV, P < .001), high-grade carcinoma (grades 2-3, P < .001), and suboptimal primary cytoreductive surgery (residual disease <1cm, P = .021). The expression level of NEDD9 varied in ovarian cancer cell lines. Multivariate analysis indicated that NEDD9 overexpression (P = .033), advanced stage (P < .001), and high-grade carcinoma (P = .01) were independent predictors of poor survival. In conclusion, NEDD9 is overexpressed and associated with an unfavorable prognosis in EOC. NEDD9 overexpression is an independent factor of poor prognosis and may serve as a potential biomarker in EOC.