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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

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 progress...

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Autores principales: Zhao, Junjie, Xu, Weidong, He, Minghui, Zhang, Zhensheng, Zeng, Shuxiong, Ma, Chong, Sun, Yinghao, Xu, Chuanliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342767/
https://www.ncbi.nlm.nih.gov/pubmed/27689332
http://dx.doi.org/10.18632/oncotarget.12315
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author Zhao, Junjie
Xu, Weidong
He, Minghui
Zhang, Zhensheng
Zeng, Shuxiong
Ma, Chong
Sun, Yinghao
Xu, Chuanliang
author_facet Zhao, Junjie
Xu, Weidong
He, Minghui
Zhang, Zhensheng
Zeng, Shuxiong
Ma, Chong
Sun, Yinghao
Xu, Chuanliang
author_sort Zhao, Junjie
collection PubMed
description 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 (T(sup)) and basal tumor tissues (T(bas)) 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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spelling pubmed-53427672017-03-28 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 Zhao, Junjie Xu, Weidong He, Minghui Zhang, Zhensheng Zeng, Shuxiong Ma, Chong Sun, Yinghao Xu, Chuanliang Oncotarget Research Paper 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 (T(sup)) and basal tumor tissues (T(bas)) 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. Impact Journals LLC 2016-09-28 /pmc/articles/PMC5342767/ /pubmed/27689332 http://dx.doi.org/10.18632/oncotarget.12315 Text en Copyright: © 2016 Zhao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhao, Junjie
Xu, Weidong
He, Minghui
Zhang, Zhensheng
Zeng, Shuxiong
Ma, Chong
Sun, Yinghao
Xu, Chuanliang
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342767/
https://www.ncbi.nlm.nih.gov/pubmed/27689332
http://dx.doi.org/10.18632/oncotarget.12315
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