High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy

BMC Cancer

Research Article

Wei Zhao¹  Bentao Shi²  Qun He³  Xinyu Yang³  Xuesong Li⁴  Gengyan Xiong⁴  Yinglu Guo⁴  Liqun Zhou⁴  Boxing Su⁴  Yuan Tang⁴  Dong Fang⁴  Zhongqiang Guo⁴ 

[1] Department of Cell Biology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, 100142, Beijing, China;Department of Urology, Peking University Shenzhen Hospital, 518036, Shenzhen, Guangdong, China;National Urological Cancer Center, Beijing& Institute of Urology, Peking University, 100034, Beijing, China;National Urological Cancer Center, Beijing& Institute of Urology, Peking University, 100034, Beijing, China;Department of Urological Pathology, Peking University First Hospital & Institute of Urology, Peking University, 100034, Beijing, China;National Urological Cancer Center, Beijing& Institute of Urology, Peking University, 100034, Beijing, China;Department of Urology, Peking University First Hospital, 100034, Beijing, China;

关键词: KPNA2;    Upper tract urothelial carcinoma;    Prognosis;    Bladder recurrence;   

DOI  :  10.1186/s12885-015-1369-8

 received in 2015-01-03, accepted in 2015-04-24,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTo analyze the expression of karyopherin alpha 2 (KPNA2) in upper tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression provides additional prognostic information following radical nephroureterectomy (RNU).MethodsA tissue microarray (TMA) containing samples from 176 patients with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression using immunohistochemistry. KPNA2 expression in normal urothelial cell line and urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA interference in vitro, the effects of KPNA2 inhibition on cellular viability, migration and apoptosis were determined.ResultsKPNA2 expression was significantly upregulated in the UTUC samples compared with the adjacent normal urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the conventional predictive factors in a multivariate analysis. Additional in vitro experiments revealed that KPNA2 expression was higher in urothelial carcinoma cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific siRNA decreased cell viability and migration and increased apoptosis in urothelial carcinoma cell lines.ConclusionsKPNA2 is a novel independent prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have undergone RNU. Moreover, these data suggest that KPNA2 may be a promising therapeutic target for UTUC.

【 授权许可】

Unknown   
© Shi et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.