Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent copy number variation in IPO11 and prognostic significance of importin-11 overexpression on poor survival
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Junjie Zhao1,2,*, Weidong Xu2,*, Minghui He3, Zhensheng Zhang2, Shuxiong Zeng2, Chong Ma2, Yinghao Sun2, Chuanliang Xu2
1Department of Urology, Yantai Yuhuangding Hospital, Yantai 264000, China
2Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
3Cancer Research Department, BGI-Shenzhen, Yantian District, Shenzhen, Guangdong 518083, China
*These authors have contributed equally to this work
Chuanliang Xu, email: firstname.lastname@example.org
Keywords: bladder cancer, tumor progression, IPO11, prognosis, whole-exome sequencing
Received: July 10, 2016 Accepted: September 06, 2016 Published: November 15, 2016
Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following its progression to muscle-invasive bladder cancer (MIBC), despite radical cystectomy with pelvic lymph node dissection combined with chemotherapy. Therefore, the discovery of novel biomarkers for predicting the progression of this disease and of therapeutic targets for preventing it is crucial. We performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and basal tumor tissues (Tbas) from 3 MIBC patients and identified previously unreported copy number variations in IPO11 that warrants further investigation as a molecular target. In addition, we identified a significant association between the absolute copy number and mRNA expression of IPO11 and found that high importin-11 expression was correlated with poor 3-year overall survival (OS), cancer-specific survival (CSS) and cancer-free survival (CFS) compared with low expression in the BCa patients. Importin-11 overexpression was also an independent risk factor for CSS and CFS in the BCa patients. Our study has revealed that IPO11 copy number amplification contributes to its overexpression and that these changes are unfavorable prognostic factors in NMIBC. Thus, IPO11 copy number amplification and importin-11 overexpression are promising biomarkers for predicting the progression and poor prognosis of patients with NMIBC.
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