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Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy

ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients an...

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Autores principales: Schroeder, Cornelia, Navid-Hill, Elham, Meiners, Jan, Hube-Magg, Claudia, Kluth, Martina, Makrypidi-Fraune, Georgia, Simon, Ronald, Büscheck, Franziska, Luebke, Andreas M., Goebel, Cosima, Lang, Dagmar S., Weidemann, Sören, Neubauer, Emily, Hinsch, Andrea, Jacobsen, Frank, Lebok, Patrick, Michl, Uwe, Pehrke, Dirk, Huland, Hartwig, Graefen, Markus, Schlomm, Thorsten, Sauter, Guido, Höflmayer, Doris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697635/
https://www.ncbi.nlm.nih.gov/pubmed/31452838
http://dx.doi.org/10.18632/oncotarget.27132
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author Schroeder, Cornelia
Navid-Hill, Elham
Meiners, Jan
Hube-Magg, Claudia
Kluth, Martina
Makrypidi-Fraune, Georgia
Simon, Ronald
Büscheck, Franziska
Luebke, Andreas M.
Goebel, Cosima
Lang, Dagmar S.
Weidemann, Sören
Neubauer, Emily
Hinsch, Andrea
Jacobsen, Frank
Lebok, Patrick
Michl, Uwe
Pehrke, Dirk
Huland, Hartwig
Graefen, Markus
Schlomm, Thorsten
Sauter, Guido
Höflmayer, Doris
author_facet Schroeder, Cornelia
Navid-Hill, Elham
Meiners, Jan
Hube-Magg, Claudia
Kluth, Martina
Makrypidi-Fraune, Georgia
Simon, Ronald
Büscheck, Franziska
Luebke, Andreas M.
Goebel, Cosima
Lang, Dagmar S.
Weidemann, Sören
Neubauer, Emily
Hinsch, Andrea
Jacobsen, Frank
Lebok, Patrick
Michl, Uwe
Pehrke, Dirk
Huland, Hartwig
Graefen, Markus
Schlomm, Thorsten
Sauter, Guido
Höflmayer, Doris
author_sort Schroeder, Cornelia
collection PubMed
description ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of TMPRSS2:ERG fusion, higher Ki67-labeling index and PTEN deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64–2.10, p < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11–1.49, p = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse.
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spelling pubmed-66976352019-08-26 Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy Schroeder, Cornelia Navid-Hill, Elham Meiners, Jan Hube-Magg, Claudia Kluth, Martina Makrypidi-Fraune, Georgia Simon, Ronald Büscheck, Franziska Luebke, Andreas M. Goebel, Cosima Lang, Dagmar S. Weidemann, Sören Neubauer, Emily Hinsch, Andrea Jacobsen, Frank Lebok, Patrick Michl, Uwe Pehrke, Dirk Huland, Hartwig Graefen, Markus Schlomm, Thorsten Sauter, Guido Höflmayer, Doris Oncotarget Research Paper ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of TMPRSS2:ERG fusion, higher Ki67-labeling index and PTEN deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64–2.10, p < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11–1.49, p = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse. Impact Journals LLC 2019-08-13 /pmc/articles/PMC6697635/ /pubmed/31452838 http://dx.doi.org/10.18632/oncotarget.27132 Text en Copyright: © 2019 Schroeder et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Schroeder, Cornelia
Navid-Hill, Elham
Meiners, Jan
Hube-Magg, Claudia
Kluth, Martina
Makrypidi-Fraune, Georgia
Simon, Ronald
Büscheck, Franziska
Luebke, Andreas M.
Goebel, Cosima
Lang, Dagmar S.
Weidemann, Sören
Neubauer, Emily
Hinsch, Andrea
Jacobsen, Frank
Lebok, Patrick
Michl, Uwe
Pehrke, Dirk
Huland, Hartwig
Graefen, Markus
Schlomm, Thorsten
Sauter, Guido
Höflmayer, Doris
Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title_full Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title_fullStr Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title_full_unstemmed Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title_short Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy
title_sort nuclear elac2 overexpression is associated with increased hazard for relapse after radical prostatectomy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697635/
https://www.ncbi.nlm.nih.gov/pubmed/31452838
http://dx.doi.org/10.18632/oncotarget.27132
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