Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer

Introduction. Survivin is an anti-apoptotic protein encoded by the baculoviral inhibitor of apoptosis repeat containing (BIRC5) gene and is upregulated in 83% of endometrial cancers. We aimed to elucidate the prognostic importance of BIRC5 expression, and evaluate survivin as a therapeutic target for endometrial cancer, by knockdown of BIRC5 and using the survivin inhibitor-YM155. Methods. RNA sequencing data in 234 patients with endometrial carcinoma was obtained from The Cancer Genome Atlas database, and analyzed using Kaplan-Meier method, log-rank test and Cox proportional hazard model. Expressions of survivin in 16 endometrial cancer cell lines were analyzed by western blotting. Knocking down effect on survivin expression was evaluated using a small interfering RNA (siRNA). The anti-proliferative and pro-apoptotic effects of YM155 were assessed with cell viability, flow cytometry, and annexin V/propidium iodide assays. Results. High expression of BIRC5 was associated with poor progression free survival (P = 0.006), and shown to be an independent prognostic factor (HR = 1.97, 95% CI = 1.29-4.5, P = 0.045). Survivin was upregulated in 14 of 16 (87.5%) endometrial cancer cell lines, compared with endometrial immortalized cells. Apoptosis was induced by knockdown of BIRC5 in all 3 cell lines examined. YM155 showed increased population of sub-G1 cells (P < 0.001) in all 16 cell lines, and IC50 values to YM155 were <50 nm in 15 cell lines. YM155 dose dependently and significantly increased the apoptotic cell population in all 16 cell lines (P < 0.001). Conclusions. Present study indicated that survivin expression is a significant prognostic factor and that survivin is a promising therapeutic target for endometrial cancer. (C) 2016 Elsevier Inc. All rights reserved.