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学科主题: 临床医学
题名:
High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy
作者: Shi, Bentao1,2; Su, Boxing2,3; Fang, Dong2,3; Tang, Yuan2,3; Xiong, Gengyan2,3; Guo, Zhongqiang2,3; He, Qun2,4,5; Yang, Xinyu2,4,5; Zhao, Wei6; Guo, Yinglu2,3; Li, Xuesong2,3; Zhou, Liqun2,3
关键词: KPNA2 ; Upper tract urothelial carcinoma ; Prognosis ; Bladder recurrence
刊名: BMC CANCER
发表日期: 2015-05-09
DOI: 10.1186/s12885-015-1369-8
卷: 15
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: UPPER URINARY-TRACT ; TRANSITIONAL-CELL CARCINOMA ; NUCLEAR-TRANSPORT RECEPTOR ; INTRAVESICAL RECURRENCE ; KARYOPHERIN ALPHA-2 ; PREDICTIVE FACTORS ; SUBUNIT ALPHA-2 ; PROTEIN IMPORT ; BREAST-CANCER ; LUNG-CANCER
英文摘要:

Background: To 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).

Methods: A 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.

Results: KPNA2 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.

Conclusions: KPNA2 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.

语种: 英语
所属项目编号: 7122183 ; BMU20120318 ; BMU20120318 ; 81172419 ; 81372746 ; A2014653 ; 201302052
项目资助者: Beijing Natural Science Foundation ; Peking University Health Science Center ; National Taiwan University, College of Medicine ; National Natural Science Foundation ; Medical Scientific Research Foundation of Guangdong Province, China ; Science and Technology Project in Shenzhen
WOS记录号: WOS:000354429700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56499
Appears in Collections:北京大学深圳医院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China
2.Peking Univ, Inst Urol, Beijing 100034, Peoples R China
3.Peking Univ, Shenzhen Hosp, Dept Urol, Shenzhen 518036, Guangdong, Peoples R China
4.Peking Univ, Beijing & Inst Urol, Natl Urol Canc Ctr, Beijing 100034, Peoples R China
5.Peking Univ, Hosp 1, Dept Urol Pathol, Beijing 100034, Peoples R China
6.Peking Univ, Dept Cell Biol, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China

Recommended Citation:
Shi, Bentao,Su, Boxing,Fang, Dong,et al. High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy[J]. BMC CANCER,2015,15.
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