Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer

Abstract The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 2...

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Autores principales:	Jan K. Hennigs, Sarah Minner, Pierre Tennstedt, Rolf Löser, Hartwig Huland, Hans Klose, Markus Graefen, Thorsten Schlomm, Guido Sauter, Carsten Bokemeyer, Friedemann Honecker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4073062c3dbe48848f9dcf0fce1a9111
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spelling	oai:doaj.org-article:4073062c3dbe48848f9dcf0fce1a91112021-12-02T14:28:21ZSubcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer10.1038/s41598-020-60064-92045-2322https://doaj.org/article/4073062c3dbe48848f9dcf0fce1a91112020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-60064-9https://doaj.org/toc/2045-2322Abstract The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.Jan K. HennigsSarah MinnerPierre TennstedtRolf LöserHartwig HulandHans KloseMarkus GraefenThorsten SchlommGuido SauterCarsten BokemeyerFriedemann HoneckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jan K. Hennigs Sarah Minner Pierre Tennstedt Rolf Löser Hartwig Huland Hans Klose Markus Graefen Thorsten Schlomm Guido Sauter Carsten Bokemeyer Friedemann Honecker Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
description	Abstract The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.
format	article
author	Jan K. Hennigs Sarah Minner Pierre Tennstedt Rolf Löser Hartwig Huland Hans Klose Markus Graefen Thorsten Schlomm Guido Sauter Carsten Bokemeyer Friedemann Honecker
author_facet	Jan K. Hennigs Sarah Minner Pierre Tennstedt Rolf Löser Hartwig Huland Hans Klose Markus Graefen Thorsten Schlomm Guido Sauter Carsten Bokemeyer Friedemann Honecker
author_sort	Jan K. Hennigs
title	Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
title_short	Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
title_full	Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
title_fullStr	Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
title_full_unstemmed	Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer
title_sort	subcellular compartmentalization of survivin is associated with biological aggressiveness and prognosis in prostate cancer
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/4073062c3dbe48848f9dcf0fce1a9111
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Subcellular Compartmentalization of Survivin is Associated with Biological Aggressiveness and Prognosis in Prostate Cancer

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