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High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer

BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples...

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Autores principales: Heumann, Asmus, Heinemann, Nina, Hube-Magg, Claudia, Lang, Dagmar S., Grupp, Katharina, Kluth, Martina, Minner, Sarah, Möller-Koop, Christina, Graefen, Markus, Heinzer, Hans, Tsourlakis, Maria Christina, Wilczak, Waldemar, Wittmer, Corinna, Jacobsen, Frank, Huland, Hartwig, Simon, Ronald, Schlomm, Thorsten, Sauter, Guido, Steurer, Stefan, Lebok, Patrick, Hinsch, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756403/
https://www.ncbi.nlm.nih.gov/pubmed/29304771
http://dx.doi.org/10.1186/s12885-017-3956-3
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author Heumann, Asmus
Heinemann, Nina
Hube-Magg, Claudia
Lang, Dagmar S.
Grupp, Katharina
Kluth, Martina
Minner, Sarah
Möller-Koop, Christina
Graefen, Markus
Heinzer, Hans
Tsourlakis, Maria Christina
Wilczak, Waldemar
Wittmer, Corinna
Jacobsen, Frank
Huland, Hartwig
Simon, Ronald
Schlomm, Thorsten
Sauter, Guido
Steurer, Stefan
Lebok, Patrick
Hinsch, Andrea
author_facet Heumann, Asmus
Heinemann, Nina
Hube-Magg, Claudia
Lang, Dagmar S.
Grupp, Katharina
Kluth, Martina
Minner, Sarah
Möller-Koop, Christina
Graefen, Markus
Heinzer, Hans
Tsourlakis, Maria Christina
Wilczak, Waldemar
Wittmer, Corinna
Jacobsen, Frank
Huland, Hartwig
Simon, Ronald
Schlomm, Thorsten
Sauter, Guido
Steurer, Stefan
Lebok, Patrick
Hinsch, Andrea
author_sort Heumann, Asmus
collection PubMed
description BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. RESULTS: BCAR1 staining was barely detectable in normal prostate glands but seen in 77.6% of 9472 interpretable cancers, including strong expression in 38.5%, moderate in 23.2% and weak in 15.9% of cases. BCAR1 up regulation was associated with positive ERG status (p < 0.0001), high Gleason score (p < 0.0001), advanced pathological tumor stage (p = 0.0082), lower preoperative PSA level (p < 0.0001), increased cell proliferation (p < 0.0001), early PSA recurrence (p = 0.0008), and predicted prognosis independently from clinico-pathological parameters available at the time of the initial biopsy. However, subset analyses revealed that the prognostic impact of BCAR1 expression was limited to ERG-negative cancer. That BCAR1 up regulation was linked to almost all analyzed deletions (p < 0.0001 each for PTEN, 5q, 6q deletion) may suggest a functional link to genomic instability. CONCLUSION: The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12885-017-3956-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-57564032018-01-09 High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer Heumann, Asmus Heinemann, Nina Hube-Magg, Claudia Lang, Dagmar S. Grupp, Katharina Kluth, Martina Minner, Sarah Möller-Koop, Christina Graefen, Markus Heinzer, Hans Tsourlakis, Maria Christina Wilczak, Waldemar Wittmer, Corinna Jacobsen, Frank Huland, Hartwig Simon, Ronald Schlomm, Thorsten Sauter, Guido Steurer, Stefan Lebok, Patrick Hinsch, Andrea BMC Cancer Research Article BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. RESULTS: BCAR1 staining was barely detectable in normal prostate glands but seen in 77.6% of 9472 interpretable cancers, including strong expression in 38.5%, moderate in 23.2% and weak in 15.9% of cases. BCAR1 up regulation was associated with positive ERG status (p < 0.0001), high Gleason score (p < 0.0001), advanced pathological tumor stage (p = 0.0082), lower preoperative PSA level (p < 0.0001), increased cell proliferation (p < 0.0001), early PSA recurrence (p = 0.0008), and predicted prognosis independently from clinico-pathological parameters available at the time of the initial biopsy. However, subset analyses revealed that the prognostic impact of BCAR1 expression was limited to ERG-negative cancer. That BCAR1 up regulation was linked to almost all analyzed deletions (p < 0.0001 each for PTEN, 5q, 6q deletion) may suggest a functional link to genomic instability. CONCLUSION: The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12885-017-3956-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-05 /pmc/articles/PMC5756403/ /pubmed/29304771 http://dx.doi.org/10.1186/s12885-017-3956-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Heumann, Asmus
Heinemann, Nina
Hube-Magg, Claudia
Lang, Dagmar S.
Grupp, Katharina
Kluth, Martina
Minner, Sarah
Möller-Koop, Christina
Graefen, Markus
Heinzer, Hans
Tsourlakis, Maria Christina
Wilczak, Waldemar
Wittmer, Corinna
Jacobsen, Frank
Huland, Hartwig
Simon, Ronald
Schlomm, Thorsten
Sauter, Guido
Steurer, Stefan
Lebok, Patrick
Hinsch, Andrea
High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title_full High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title_fullStr High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title_full_unstemmed High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title_short High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer
title_sort high bcar1 expression is associated with early psa recurrence in erg negative prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756403/
https://www.ncbi.nlm.nih.gov/pubmed/29304771
http://dx.doi.org/10.1186/s12885-017-3956-3
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