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High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer

INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value o...

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Autores principales: Sikic, Danijel, Breyer, Johannes, Hartmann, Arndt, Burger, Maximilian, Erben, Philipp, Denzinger, Stefan, Eckstein, Markus, Stöhr, Robert, Wach, Sven, Wullich, Bernd, Keck, Bastian, Wirtz, Ralph M., Otto, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367846/
https://www.ncbi.nlm.nih.gov/pubmed/28342317
http://dx.doi.org/10.1016/j.tranon.2017.01.013
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author Sikic, Danijel
Breyer, Johannes
Hartmann, Arndt
Burger, Maximilian
Erben, Philipp
Denzinger, Stefan
Eckstein, Markus
Stöhr, Robert
Wach, Sven
Wullich, Bernd
Keck, Bastian
Wirtz, Ralph M.
Otto, Wolfgang
author_facet Sikic, Danijel
Breyer, Johannes
Hartmann, Arndt
Burger, Maximilian
Erben, Philipp
Denzinger, Stefan
Eckstein, Markus
Stöhr, Robert
Wach, Sven
Wullich, Bernd
Keck, Bastian
Wirtz, Ralph M.
Otto, Wolfgang
author_sort Sikic, Danijel
collection PubMed
description INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (r(s): 0.3171, P < .0001) as well as a negative association with multifocal tumors (r(s): 0.1478, P < .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS: AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.
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spelling pubmed-53678462017-03-29 High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer Sikic, Danijel Breyer, Johannes Hartmann, Arndt Burger, Maximilian Erben, Philipp Denzinger, Stefan Eckstein, Markus Stöhr, Robert Wach, Sven Wullich, Bernd Keck, Bastian Wirtz, Ralph M. Otto, Wolfgang Transl Oncol Original article INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (r(s): 0.3171, P < .0001) as well as a negative association with multifocal tumors (r(s): 0.1478, P < .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS: AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression. Neoplasia Press 2017-03-22 /pmc/articles/PMC5367846/ /pubmed/28342317 http://dx.doi.org/10.1016/j.tranon.2017.01.013 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Sikic, Danijel
Breyer, Johannes
Hartmann, Arndt
Burger, Maximilian
Erben, Philipp
Denzinger, Stefan
Eckstein, Markus
Stöhr, Robert
Wach, Sven
Wullich, Bernd
Keck, Bastian
Wirtz, Ralph M.
Otto, Wolfgang
High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title_full High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title_fullStr High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title_full_unstemmed High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title_short High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
title_sort high androgen receptor mrna expression is independently associated with prolonged cancer-specific and recurrence-free survival in stage t1 bladder cancer
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367846/
https://www.ncbi.nlm.nih.gov/pubmed/28342317
http://dx.doi.org/10.1016/j.tranon.2017.01.013
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