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Published in: BMC Cancer 1/2020

01-12-2020 | Prostate Cancer | Research article

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

Authors: Morton Freytag, Martina Kluth, Elena Bady, Claudia Hube-Magg, Georgia Makrypidi-Fraune, Hans Heinzer, Doris Höflmayer, Sören Weidemann, Ria Uhlig, Hartwig Huland, Markus Graefen, Christian Bernreuther, Corinna Wittmer, Maria Christina Tsourlakis, Sarah Minner, David Dum, Andrea Hinsch, Andreas M. Luebke, Ronald Simon, Guido Sauter, Thorsten Schlomm, Katharina Möller

Published in: BMC Cancer | Issue 1/2020

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Abstract

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.
Appendix
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Metadata
Title
Epithelial splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) upregulation predicts poor prognosis in prostate cancer
Authors
Morton Freytag
Martina Kluth
Elena Bady
Claudia Hube-Magg
Georgia Makrypidi-Fraune
Hans Heinzer
Doris Höflmayer
Sören Weidemann
Ria Uhlig
Hartwig Huland
Markus Graefen
Christian Bernreuther
Corinna Wittmer
Maria Christina Tsourlakis
Sarah Minner
David Dum
Andrea Hinsch
Andreas M. Luebke
Ronald Simon
Guido Sauter
Thorsten Schlomm
Katharina Möller
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-07682-8

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