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Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specim...

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Autores principales: Spethmann, Tanja, Böckelmann, Lukas Clemens, Labitzky, Vera, Ahlers, Ann‐Kristin, Schröder‐Schwarz, Jennifer, Bonk, Sarah, Simon, Ronald, Sauter, Guido, Huland, Hartwig, Kypta, Robert, Schumacher, Udo, Lange, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253102/
https://www.ncbi.nlm.nih.gov/pubmed/33533127
http://dx.doi.org/10.1002/1878-0261.12922
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author Spethmann, Tanja
Böckelmann, Lukas Clemens
Labitzky, Vera
Ahlers, Ann‐Kristin
Schröder‐Schwarz, Jennifer
Bonk, Sarah
Simon, Ronald
Sauter, Guido
Huland, Hartwig
Kypta, Robert
Schumacher, Udo
Lange, Tobias
author_facet Spethmann, Tanja
Böckelmann, Lukas Clemens
Labitzky, Vera
Ahlers, Ann‐Kristin
Schröder‐Schwarz, Jennifer
Bonk, Sarah
Simon, Ronald
Sauter, Guido
Huland, Hartwig
Kypta, Robert
Schumacher, Udo
Lange, Tobias
author_sort Spethmann, Tanja
collection PubMed
description Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.
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spelling pubmed-82531022021-07-13 Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets Spethmann, Tanja Böckelmann, Lukas Clemens Labitzky, Vera Ahlers, Ann‐Kristin Schröder‐Schwarz, Jennifer Bonk, Sarah Simon, Ronald Sauter, Guido Huland, Hartwig Kypta, Robert Schumacher, Udo Lange, Tobias Mol Oncol Research Articles Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets. John Wiley and Sons Inc. 2021-02-17 2021-07 /pmc/articles/PMC8253102/ /pubmed/33533127 http://dx.doi.org/10.1002/1878-0261.12922 Text en © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Spethmann, Tanja
Böckelmann, Lukas Clemens
Labitzky, Vera
Ahlers, Ann‐Kristin
Schröder‐Schwarz, Jennifer
Bonk, Sarah
Simon, Ronald
Sauter, Guido
Huland, Hartwig
Kypta, Robert
Schumacher, Udo
Lange, Tobias
Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title_full Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title_fullStr Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title_full_unstemmed Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title_short Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
title_sort opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253102/
https://www.ncbi.nlm.nih.gov/pubmed/33533127
http://dx.doi.org/10.1002/1878-0261.12922
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