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

• Survivin expression was associated with poor prognosis in endometrial cancer.
• YM155, a survivin inhibitor, induced apoptosis in endometrial cancer cells.
• Survivin may serve as a a promising therapeutic target for endometrial cancer.

IntroductionSurvivin 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 knock-down of BIRC5 and using the survivin inhibitor-YM155.MethodsRNA 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.ResultsHigh 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).ConclusionsPresent study indicated that survivin expression is a significant prognostic factor and that survivin is a promising therapeutic target for endometrial cancer.