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High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer
Hook microtubule-tethering protein 3 (HOOK3) is an adaptor protein for microtubule-dependent intracellular vesicle and protein trafficking. In order to assess the role of HOOK3 in prostate cancer we analyzed HOOK3 expression by immunohistochemistry on a TMA containing more than 12,400 prostate cance...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521853/ https://www.ncbi.nlm.nih.gov/pubmed/26230842 http://dx.doi.org/10.1371/journal.pone.0134614 |
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author | Melling, Nathaniel Harutyunyan, Levon Hube-Magg, Claudia Kluth, Martina Simon, Ronald Lebok, Patrick Minner, Sarah Tsourlakis, Maria Christina Koop, Christina Graefen, Markus Adam, Meike Haese, Alexander Wittmer, Corinna Steurer, Stefan Izbicki, Jakob Sauter, Guido Wilczak, Waldemar Schlomm, Thorsten Krech, Till |
author_facet | Melling, Nathaniel Harutyunyan, Levon Hube-Magg, Claudia Kluth, Martina Simon, Ronald Lebok, Patrick Minner, Sarah Tsourlakis, Maria Christina Koop, Christina Graefen, Markus Adam, Meike Haese, Alexander Wittmer, Corinna Steurer, Stefan Izbicki, Jakob Sauter, Guido Wilczak, Waldemar Schlomm, Thorsten Krech, Till |
author_sort | Melling, Nathaniel |
collection | PubMed |
description | Hook microtubule-tethering protein 3 (HOOK3) is an adaptor protein for microtubule-dependent intracellular vesicle and protein trafficking. In order to assess the role of HOOK3 in prostate cancer we analyzed HOOK3 expression by immunohistochemistry on a TMA containing more than 12,400 prostate cancers. Results were compared to tumor phenotype and PSA recurrence as well as aberrations possibly defining relevant molecular subtypes such as ERG status and deletions of 3p13, 5q21, 6q15 and PTEN. HOOK3 immunostaining was negative in normal luminal cells of prostate epithelium, whereas 53.3% of 10,572 interpretable cancers showed HOOK3 expression, which was considered low in 36.4% and high in 16.9% of cases. High-level HOOK3 expression was linked to advanced tumor stage, high Gleason score, high proliferation index, positive lymph node stage, and PSA recurrence (p<0.0001 each). The prognostic role of HOOK3 expression was independent of established clinico-pathological parameters both in preoperative and postoperative settings. Comparisons with molecular features were performed to draw conclusions on the potential function of HOOK3 in the prostate. A strong association with all examined deletions is consistent with a role of HOOK3 for maintaining genomic integrity by contributing to proper centrosome assembly. Finding HOOK3 expression in 74% of ERG positive but in only 38% of ERG negative cancers (p<0.0001) further suggests functional interactions between these genes. In conclusion, the results of our study identify HOOK3 as a strong candidate prognostic marker with a possible role in maintaining genomic integrity in prostate cancer, which may have potential for inclusion into clinical routine assays. |
format | Online Article Text |
id | pubmed-4521853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45218532015-08-06 High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer Melling, Nathaniel Harutyunyan, Levon Hube-Magg, Claudia Kluth, Martina Simon, Ronald Lebok, Patrick Minner, Sarah Tsourlakis, Maria Christina Koop, Christina Graefen, Markus Adam, Meike Haese, Alexander Wittmer, Corinna Steurer, Stefan Izbicki, Jakob Sauter, Guido Wilczak, Waldemar Schlomm, Thorsten Krech, Till PLoS One Research Article Hook microtubule-tethering protein 3 (HOOK3) is an adaptor protein for microtubule-dependent intracellular vesicle and protein trafficking. In order to assess the role of HOOK3 in prostate cancer we analyzed HOOK3 expression by immunohistochemistry on a TMA containing more than 12,400 prostate cancers. Results were compared to tumor phenotype and PSA recurrence as well as aberrations possibly defining relevant molecular subtypes such as ERG status and deletions of 3p13, 5q21, 6q15 and PTEN. HOOK3 immunostaining was negative in normal luminal cells of prostate epithelium, whereas 53.3% of 10,572 interpretable cancers showed HOOK3 expression, which was considered low in 36.4% and high in 16.9% of cases. High-level HOOK3 expression was linked to advanced tumor stage, high Gleason score, high proliferation index, positive lymph node stage, and PSA recurrence (p<0.0001 each). The prognostic role of HOOK3 expression was independent of established clinico-pathological parameters both in preoperative and postoperative settings. Comparisons with molecular features were performed to draw conclusions on the potential function of HOOK3 in the prostate. A strong association with all examined deletions is consistent with a role of HOOK3 for maintaining genomic integrity by contributing to proper centrosome assembly. Finding HOOK3 expression in 74% of ERG positive but in only 38% of ERG negative cancers (p<0.0001) further suggests functional interactions between these genes. In conclusion, the results of our study identify HOOK3 as a strong candidate prognostic marker with a possible role in maintaining genomic integrity in prostate cancer, which may have potential for inclusion into clinical routine assays. Public Library of Science 2015-07-31 /pmc/articles/PMC4521853/ /pubmed/26230842 http://dx.doi.org/10.1371/journal.pone.0134614 Text en © 2015 Melling et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Melling, Nathaniel Harutyunyan, Levon Hube-Magg, Claudia Kluth, Martina Simon, Ronald Lebok, Patrick Minner, Sarah Tsourlakis, Maria Christina Koop, Christina Graefen, Markus Adam, Meike Haese, Alexander Wittmer, Corinna Steurer, Stefan Izbicki, Jakob Sauter, Guido Wilczak, Waldemar Schlomm, Thorsten Krech, Till High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title | High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title_full | High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title_fullStr | High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title_full_unstemmed | High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title_short | High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer |
title_sort | high-level hook3 expression is an independent predictor of poor prognosis associated with genomic instability in prostate cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521853/ https://www.ncbi.nlm.nih.gov/pubmed/26230842 http://dx.doi.org/10.1371/journal.pone.0134614 |
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