14-3-3 zeta Overexpression is Associated with Poor Prognosis in Ovarian Cancer

Abstract

Purpose: 14-3-3 zeta regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3 zeta is associated with ovarian cancer prognosis. Materials and Methods: We examined 14-3-3 zeta expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3 zeta expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTSbased assay following cisplatin treatment. Results: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3 zeta expression, and 14-3-3 zeta overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3 zeta overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3 zeta expression group, but not reached in the low 14-3-3 zeta expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3 zeta by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. Conclusion: 14-3-3 zeta overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3 zeta could be a therapeutic option that enhances the antitumor activity of cisplatin.