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Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers
The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 cl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265544/ https://www.ncbi.nlm.nih.gov/pubmed/32488048 http://dx.doi.org/10.1038/s41598-020-65772-w |
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author | Marx, Andreas Schumann, Aljoscha Höflmayer, Doris Bady, Elena Hube-Magg, Claudia Möller, Katharina Tsourlakis, Maria Christina Steurer, Stefan Büscheck, Franziska Eichenauer, Till Clauditz, Till S. Graefen, Markus Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Polonski, Adam |
author_facet | Marx, Andreas Schumann, Aljoscha Höflmayer, Doris Bady, Elena Hube-Magg, Claudia Möller, Katharina Tsourlakis, Maria Christina Steurer, Stefan Büscheck, Franziska Eichenauer, Till Clauditz, Till S. Graefen, Markus Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Polonski, Adam |
author_sort | Marx, Andreas |
collection | PubMed |
description | The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus. |
format | Online Article Text |
id | pubmed-7265544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72655442020-06-05 Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers Marx, Andreas Schumann, Aljoscha Höflmayer, Doris Bady, Elena Hube-Magg, Claudia Möller, Katharina Tsourlakis, Maria Christina Steurer, Stefan Büscheck, Franziska Eichenauer, Till Clauditz, Till S. Graefen, Markus Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Polonski, Adam Sci Rep Article The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus. Nature Publishing Group UK 2020-06-02 /pmc/articles/PMC7265544/ /pubmed/32488048 http://dx.doi.org/10.1038/s41598-020-65772-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Marx, Andreas Schumann, Aljoscha Höflmayer, Doris Bady, Elena Hube-Magg, Claudia Möller, Katharina Tsourlakis, Maria Christina Steurer, Stefan Büscheck, Franziska Eichenauer, Till Clauditz, Till S. Graefen, Markus Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Polonski, Adam Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title | Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title_full | Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title_fullStr | Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title_full_unstemmed | Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title_short | Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers |
title_sort | up regulation of the hippo signalling effector yap1 is linked to early biochemical recurrence in prostate cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265544/ https://www.ncbi.nlm.nih.gov/pubmed/32488048 http://dx.doi.org/10.1038/s41598-020-65772-w |
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