Androgen receptor profiling predicts prostate cancer outcome

Abstract Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high‐risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, w...

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Main Authors: Suzan Stelloo, Ekaterina Nevedomskaya, Henk G van der Poel, Jeroen de Jong, Geert JLH van Leenders, Guido Jenster, Lodewyk FA Wessels, Andries M Bergman, Wilbert Zwart
Format: Article
Language:English
Published: Springer Nature 2015-09-01
Series:EMBO Molecular Medicine
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Online Access:https://doi.org/10.15252/emmm.201505424
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author Suzan Stelloo
Ekaterina Nevedomskaya
Henk G van der Poel
Jeroen de Jong
Geert JLH van Leenders
Guido Jenster
Lodewyk FA Wessels
Andries M Bergman
Wilbert Zwart
author_facet Suzan Stelloo
Ekaterina Nevedomskaya
Henk G van der Poel
Jeroen de Jong
Geert JLH van Leenders
Guido Jenster
Lodewyk FA Wessels
Andries M Bergman
Wilbert Zwart
author_sort Suzan Stelloo
collection DOAJ
description Abstract Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high‐risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology.
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institution Kabale University
issn 1757-4676
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language English
publishDate 2015-09-01
publisher Springer Nature
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series EMBO Molecular Medicine
spelling doaj-art-90f6ed52c3cb49288248300a76c053b72025-08-20T04:03:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842015-09-017111450146410.15252/emmm.201505424Androgen receptor profiling predicts prostate cancer outcomeSuzan Stelloo0Ekaterina Nevedomskaya1Henk G van der Poel2Jeroen de Jong3Geert JLH van Leenders4Guido Jenster5Lodewyk FA Wessels6Andries M Bergman7Wilbert Zwart8Division of Molecular Pathology, The Netherlands Cancer InstituteDivision of Molecular Pathology, The Netherlands Cancer InstituteDivision of Urology, The Netherlands Cancer InstituteDivision of Pathology, The Netherlands Cancer InstituteDepartment of Pathology, Josephine Nefkens Institute, Erasmus Medical CenterDepartment of Urology, Josephine Nefkens Institute, Erasmus Medical CenterDivision of Molecular Carcinogenesis, The Netherlands Cancer InstituteDivision of Medical Oncology, The Netherlands Cancer InstituteDivision of Molecular Pathology, The Netherlands Cancer InstituteAbstract Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high‐risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology.https://doi.org/10.15252/emmm.201505424androgen receptor profilingChIP‐seqcompanion diagnostics for prostate cancerFAIRE‐seqtreatment prediction
spellingShingle Suzan Stelloo
Ekaterina Nevedomskaya
Henk G van der Poel
Jeroen de Jong
Geert JLH van Leenders
Guido Jenster
Lodewyk FA Wessels
Andries M Bergman
Wilbert Zwart
Androgen receptor profiling predicts prostate cancer outcome
EMBO Molecular Medicine
androgen receptor profiling
ChIP‐seq
companion diagnostics for prostate cancer
FAIRE‐seq
treatment prediction
title Androgen receptor profiling predicts prostate cancer outcome
title_full Androgen receptor profiling predicts prostate cancer outcome
title_fullStr Androgen receptor profiling predicts prostate cancer outcome
title_full_unstemmed Androgen receptor profiling predicts prostate cancer outcome
title_short Androgen receptor profiling predicts prostate cancer outcome
title_sort androgen receptor profiling predicts prostate cancer outcome
topic androgen receptor profiling
ChIP‐seq
companion diagnostics for prostate cancer
FAIRE‐seq
treatment prediction
url https://doi.org/10.15252/emmm.201505424
work_keys_str_mv AT suzanstelloo androgenreceptorprofilingpredictsprostatecanceroutcome
AT ekaterinanevedomskaya androgenreceptorprofilingpredictsprostatecanceroutcome
AT henkgvanderpoel androgenreceptorprofilingpredictsprostatecanceroutcome
AT jeroendejong androgenreceptorprofilingpredictsprostatecanceroutcome
AT geertjlhvanleenders androgenreceptorprofilingpredictsprostatecanceroutcome
AT guidojenster androgenreceptorprofilingpredictsprostatecanceroutcome
AT lodewykfawessels androgenreceptorprofilingpredictsprostatecanceroutcome
AT andriesmbergman androgenreceptorprofilingpredictsprostatecanceroutcome
AT wilbertzwart androgenreceptorprofilingpredictsprostatecanceroutcome