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: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-09-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201505424 |
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| _version_ | 1849234871693606912 |
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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. |
| format | Article |
| id | doaj-art-90f6ed52c3cb49288248300a76c053b7 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2015-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| 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 |
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