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High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer

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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.

in: PLOS ONE, Jahrgang 10, Nr. 7, 2015, S. e0134614.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Melling, N, Harutyunyan, L, Hube-Magg, C, Kluth, M, Simon, R, Lebok, P, Minner, S, Tsourlakis, MC, Koop, C, Graefen, M, Adam, M, Haese, A, Wittmer, C, Steurer, S, Izbicki, J, Sauter, G, Wilczak, W, Schlomm, T & Krech, T 2015, 'High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer', PLOS ONE, Jg. 10, Nr. 7, S. e0134614. https://doi.org/10.1371/journal.pone.0134614

APA

Melling, N., Harutyunyan, L., Hube-Magg, C., Kluth, M., Simon, R., Lebok, P., Minner, S., Tsourlakis, M. C., Koop, C., Graefen, M., Adam, M., Haese, A., Wittmer, C., Steurer, S., Izbicki, J., Sauter, G., Wilczak, W., Schlomm, T., & Krech, T. (2015). High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer. PLOS ONE, 10(7), e0134614. https://doi.org/10.1371/journal.pone.0134614

Vancouver

Melling N, Harutyunyan L, Hube-Magg C, Kluth M, Simon R, Lebok P et al. High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer. PLOS ONE. 2015;10(7):e0134614. https://doi.org/10.1371/journal.pone.0134614

Bibtex

@article{5211f2222f8e47498de97795481247e4,
title = "High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer",
abstract = "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.",
author = "Nathaniel Melling and Levon Harutyunyan and Claudia Hube-Magg and Martina Kluth and Ronald Simon and Patrick Lebok and Sarah Minner and Tsourlakis, {Maria Christina} and Christina Koop and Markus Graefen and Meike Adam and Alexander Haese and Corinna Wittmer and Stefan Steurer and Jakob Izbicki and Guido Sauter and Waldemar Wilczak and Thorsten Schlomm and Till Krech",
year = "2015",
doi = "10.1371/journal.pone.0134614",
language = "English",
volume = "10",
pages = "e0134614",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - High-Level HOOK3 Expression Is an Independent Predictor of Poor Prognosis Associated with Genomic Instability in Prostate Cancer

AU - Melling, Nathaniel

AU - Harutyunyan, Levon

AU - Hube-Magg, Claudia

AU - Kluth, Martina

AU - Simon, Ronald

AU - Lebok, Patrick

AU - Minner, Sarah

AU - Tsourlakis, Maria Christina

AU - Koop, Christina

AU - Graefen, Markus

AU - Adam, Meike

AU - Haese, Alexander

AU - Wittmer, Corinna

AU - Steurer, Stefan

AU - Izbicki, Jakob

AU - Sauter, Guido

AU - Wilczak, Waldemar

AU - Schlomm, Thorsten

AU - Krech, Till

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0134614

DO - 10.1371/journal.pone.0134614

M3 - SCORING: Journal article

C2 - 26230842

VL - 10

SP - e0134614

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 7

ER -