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

被引：26

作者：

Chuwa, Agapiti Hipoliti ^{[1
]}

Sone, Kenbun ^{[1
]}

Oda, Katsutoshi ^{[1
]}

Ikeda, Yuji ^{[1
]}

Fukuda, Tomohiko ^{[1
]}

Wada-Hiraike, Osamu ^{[1
]}

Inaba, Kanako ^{[1
]}

Makii, Chinami ^{[1
]}

Takeuchi, Makoto ^{[1
]}

Oki, Shinya ^{[1
]}

Miyasaka, Aki ^{[1
]}

Kashiyama, Tomoko ^{[1
]}

Arimoto, Takahide ^{[1
]}

Kuramoto, Hiroyuki ^{[2
]}

Kawana, Kei ^{[1
]}

Yano, Tetsu ^{[3
]}

Osuga, Yutaka ^{[1
]}

Fujii, Tomoyuki ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Obstet & Gynecol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan

[2] Kanagawa Hlth Serv Assoc, Yokohama, Kanagawa, Japan

[3] Natl Ctr Global Hlth & Med, Dept Obstet & Gynecol, Tokyo, Japan

来源：

GYNECOLOGIC ONCOLOGY | 2016年 / 141卷 / 03期

关键词：

Survivin; Prognosis; Apoptosis; Molecular targeted therapy; Endometrial cancer; PHASE-II; YM155; EXPRESSION; INHIBITOR; CARCINOMA; APOPTOSIS; CELLS; MULTICENTER; SUPPRESSOR; BIOMARKER;

D O I：

10.1016/j.ygyno.2016.04.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：564 / 569

页数：6

共 40 条

[1] Lack of Relation of Survivin Gene Expression with Survival and Surgical Prognostic Factors in Endometrial Carcinoma Patients [J].