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Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer

BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimat...

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Autores principales: Freytag, Morton, Kluth, Martina, Bady, Elena, Hube-Magg, Claudia, Makrypidi-Fraune, Georgia, Heinzer, Hans, Höflmayer, Doris, Weidemann, Sören, Uhlig, Ria, Huland, Hartwig, Graefen, Markus, Bernreuther, Christian, Wittmer, Corinna, Tsourlakis, Maria Christina, Minner, Sarah, Dum, David, Hinsch, Andrea, Luebke, Andreas M., Simon, Ronald, Sauter, Guido, Schlomm, Thorsten, Möller, Katharina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749503/
https://www.ncbi.nlm.nih.gov/pubmed/33339518
http://dx.doi.org/10.1186/s12885-020-07682-8
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author Freytag, Morton
Kluth, Martina
Bady, Elena
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Heinzer, Hans
Höflmayer, Doris
Weidemann, Sören
Uhlig, Ria
Huland, Hartwig
Graefen, Markus
Bernreuther, Christian
Wittmer, Corinna
Tsourlakis, Maria Christina
Minner, Sarah
Dum, David
Hinsch, Andrea
Luebke, Andreas M.
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Möller, Katharina
author_facet Freytag, Morton
Kluth, Martina
Bady, Elena
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Heinzer, Hans
Höflmayer, Doris
Weidemann, Sören
Uhlig, Ria
Huland, Hartwig
Graefen, Markus
Bernreuther, Christian
Wittmer, Corinna
Tsourlakis, Maria Christina
Minner, Sarah
Dum, David
Hinsch, Andrea
Luebke, Andreas M.
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Möller, Katharina
author_sort Freytag, Morton
collection PubMed
description BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. METHODS: A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. RESULTS: Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features. CONCLUSIONS: Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.
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spelling pubmed-77495032020-12-21 Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer Freytag, Morton Kluth, Martina Bady, Elena Hube-Magg, Claudia Makrypidi-Fraune, Georgia Heinzer, Hans Höflmayer, Doris Weidemann, Sören Uhlig, Ria Huland, Hartwig Graefen, Markus Bernreuther, Christian Wittmer, Corinna Tsourlakis, Maria Christina Minner, Sarah Dum, David Hinsch, Andrea Luebke, Andreas M. Simon, Ronald Sauter, Guido Schlomm, Thorsten Möller, Katharina BMC Cancer Research Article BACKGROUND: Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. METHODS: A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. RESULTS: Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p < 0.0001 each). Expression of ESRPs was significantly linked to 11 (ESRP1)/9 (ESRP2) of 11 analyzed deletions in all cancers and to 8 (ESRP1)/9 (ESRP2) of 11 deletions in ERG-negative cancers portending a link to genomic instability. Combined ESRPs expression analysis suggested an additive effect and showed the worst prognosis for cancers with high ESRP1 and ESRP2 expression. Multivariate analyses revealed that the prognostic impact of ESRP1, ESRP2 and combined ESRP1/ESRP2 expression was independent of all established pre- and postoperative prognostic features. CONCLUSIONS: Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application. BioMed Central 2020-12-18 /pmc/articles/PMC7749503/ /pubmed/33339518 http://dx.doi.org/10.1186/s12885-020-07682-8 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research Article
Freytag, Morton
Kluth, Martina
Bady, Elena
Hube-Magg, Claudia
Makrypidi-Fraune, Georgia
Heinzer, Hans
Höflmayer, Doris
Weidemann, Sören
Uhlig, Ria
Huland, Hartwig
Graefen, Markus
Bernreuther, Christian
Wittmer, Corinna
Tsourlakis, Maria Christina
Minner, Sarah
Dum, David
Hinsch, Andrea
Luebke, Andreas M.
Simon, Ronald
Sauter, Guido
Schlomm, Thorsten
Möller, Katharina
Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title_full Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title_fullStr Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title_full_unstemmed Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title_short Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
title_sort epithelial splicing regulatory protein 1 and 2 (esrp1 and esrp2) upregulation predicts poor prognosis in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749503/
https://www.ncbi.nlm.nih.gov/pubmed/33339518
http://dx.doi.org/10.1186/s12885-020-07682-8
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