High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer

The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurre...

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Main Authors: Danijel Sikic, Helge Taubert, Ralph M. Wirtz, Johannes Breyer, Markus Eckstein, Veronika Weyerer, Jennifer Kubon, Philipp Erben, Christian Bolenz, Maximilian Burger, Arndt Hartmann, Bernd Wullich, Sven Wach, Bastian Keck
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Language:English
Published: MDPI AG 2021-06-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/11/7/642
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author Danijel Sikic
Helge Taubert
Ralph M. Wirtz
Johannes Breyer
Markus Eckstein
Veronika Weyerer
Jennifer Kubon
Philipp Erben
Christian Bolenz
Maximilian Burger
Arndt Hartmann
Bernd Wullich
Sven Wach
Bastian Keck
author_facet Danijel Sikic
Helge Taubert
Ralph M. Wirtz
Johannes Breyer
Markus Eckstein
Veronika Weyerer
Jennifer Kubon
Philipp Erben
Christian Bolenz
Maximilian Burger
Arndt Hartmann
Bernd Wullich
Sven Wach
Bastian Keck
author_sort Danijel Sikic
collection DOAJ
description The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456; <i>p</i> < 0.001). AR (<i>p</i> = 0.053) and KRT5 (<i>p</i> = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (<i>p</i> = 0.020) and OS (<i>p</i> = 0.015) and a trend towards longer RFS (<i>p</i> = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (<i>p</i> = 0.033), CSS (<i>p</i> = 0.029) and OS (<i>p</i> = 0.030), while high KRT20 expression was associated with reduced RFS (<i>p</i> = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (<i>p</i> = 0.041). Women showed significantly longer OS in cases with high AR expression (<i>p</i> = 0.011). High AR was associated with significantly improved CSS in males (<i>p</i> = 0.044) and patients with instillation therapy (<i>p</i> = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (<i>p</i> = 0.021), CSS (<i>p</i> = 0.014) and OS (<i>p</i> = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (<i>p</i> = 0.003) or KRT20 (<i>p</i> = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.
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spelling doaj.art-201545d6fae9422d80d7391325d097d22023-11-22T02:31:14ZengMDPI AGLife2075-17292021-06-0111764210.3390/life11070642High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder CancerDanijel Sikic0Helge Taubert1Ralph M. Wirtz2Johannes Breyer3Markus Eckstein4Veronika Weyerer5Jennifer Kubon6Philipp Erben7Christian Bolenz8Maximilian Burger9Arndt Hartmann10Bernd Wullich11Sven Wach12Bastian Keck13Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanySTRATIFYER Molecular Pathology GmbH, 541713 Cologne, GermanyCaritas St. Josef Medical Center, Department of Urology, University of Regensburg, 93053 Regensburg, GermanyComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, GermanyComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, GermanyDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Urology and Urosurgery, University Medical Centre Mannheim, 68167 Mannheim, GermanyDepartment of Urology and Pediatric Urology, University Hospital Ulm, 89081 Ulm, GermanyCaritas St. Josef Medical Center, Department of Urology, University of Regensburg, 93053 Regensburg, GermanyComprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, GermanyDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, GermanyThe role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456; <i>p</i> < 0.001). AR (<i>p</i> = 0.053) and KRT5 (<i>p</i> = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (<i>p</i> = 0.020) and OS (<i>p</i> = 0.015) and a trend towards longer RFS (<i>p</i> = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (<i>p</i> = 0.033), CSS (<i>p</i> = 0.029) and OS (<i>p</i> = 0.030), while high KRT20 expression was associated with reduced RFS (<i>p</i> = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (<i>p</i> = 0.041). Women showed significantly longer OS in cases with high AR expression (<i>p</i> = 0.011). High AR was associated with significantly improved CSS in males (<i>p</i> = 0.044) and patients with instillation therapy (<i>p</i> = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (<i>p</i> = 0.021), CSS (<i>p</i> = 0.014) and OS (<i>p</i> = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (<i>p</i> = 0.003) or KRT20 (<i>p</i> = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.https://www.mdpi.com/2075-1729/11/7/642androgen receptorbladder cancerKRT5KRT20mRNANMIBC
spellingShingle Danijel Sikic
Helge Taubert
Ralph M. Wirtz
Johannes Breyer
Markus Eckstein
Veronika Weyerer
Jennifer Kubon
Philipp Erben
Christian Bolenz
Maximilian Burger
Arndt Hartmann
Bernd Wullich
Sven Wach
Bastian Keck
High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
Life
androgen receptor
bladder cancer
KRT5
KRT20
mRNA
NMIBC
title High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
title_full High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
title_fullStr High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
title_full_unstemmed High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
title_short High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
title_sort high androgen receptor mrna expression is associated with improved outcome in patients with high risk non muscle invasive bladder cancer
topic androgen receptor
bladder cancer
KRT5
KRT20
mRNA
NMIBC
url https://www.mdpi.com/2075-1729/11/7/642
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