title: High expression of KPNA2 defines poor prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
abstract: 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.
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China. meiliriji12@yeah.net.|National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. meiliriji12@yeah.net.
authors.forename: Bentao
authors.initials: B
authors.lastname: Shi
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. meiliriji12@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. meiliriji12@yeah.net.
authors.forename: Boxing
authors.initials: B
authors.lastname: Su
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. danzi34@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. danzi34@yeah.net.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. yasilandai12@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. yasilandai12@yeah.net.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. jiyishentan12@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. jiyishentan12@yeah.net.
authors.forename: Gengyan
authors.initials: G
authors.lastname: Xiong
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. huangxiaominghua@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. huangxiaominghua@yeah.net.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Guo
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. meilijuan12@yeah.net.|Department of Urological Pathology, Peking University First Hospital & Institute of Urology, Peking University, Beijing, 100034, China. meilijuan12@yeah.net.
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. liyuehua3123@yeah.net.|Department of Urological Pathology, Peking University First Hospital & Institute of Urology, Peking University, Beijing, 100034, China. liyuehua3123@yeah.net.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, 100142, China. chenxiaojun56@yeah.net.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. chencuiqin89@yeah.net.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. chencuiqin89@yeah.net.
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. xuesongli123@sina.cn.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. xuesongli123@sina.cn.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: National Urological Cancer Center, Beijing& Institute of Urology, Peking University, Beijing, 100034, China. zhouliqunmail@sina.com.|Department of Urology, Peking University First Hospital, Beijing, 100034, China. zhouliqunmail@sina.com.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality; D009392:Nephrectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D014513:Ureter / Q000473:pathology / Q000601:surgery; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C490630:KPNA2 protein, human; D028901:alpha Karyopherins