Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer

Numerous changes in epigenetic mechanisms have been described in various types of tumors. In search for new biomarkers, we investigated the expression of Polycomb-group (PcG) proteins EZH2, BMI1 and SUZ12 and associated histone modification H3K27me3 in colorectal cancer. Nuclear expression of PcG pr...

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Main Authors:	Benard, Anne, Goossens-Beumer, Inès J., van Hoesel, Anneke Q., Horati, Hamed, Putter, Hein, Zeestraten, Eliane C. M., van de Velde, Cornelis J. H., Kuppen, Peter J. K.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171510/

id	pubmed-4171510
recordtype	oai_dc
spelling	pubmed-41715102014-09-25 Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer Benard, Anne Goossens-Beumer, Inès J. van Hoesel, Anneke Q. Horati, Hamed Putter, Hein Zeestraten, Eliane C. M. van de Velde, Cornelis J. H. Kuppen, Peter J. K. Research Article Numerous changes in epigenetic mechanisms have been described in various types of tumors. In search for new biomarkers, we investigated the expression of Polycomb-group (PcG) proteins EZH2, BMI1 and SUZ12 and associated histone modification H3K27me3 in colorectal cancer. Nuclear expression of PcG proteins and histone modification H3K27me3 were immunohistochemically (IHC) stained on a tissue microarray (TMA), including 247 tumor tissues and 47 normal tissues, and scored using the semi-automated Ariol system. Tumor tissues showed higher expression of EZH2 (p = 0.05) and H3K27me3 (p<0.001) as compared to their normal counterparts. Combined marker trend analyses indicated that an increase in the number of markers showing high expression was associated with better prognosis. High expression of all four markers in the combined marker analyses was correlated with the best patient survival and the longest recurrence-free survival, with overall survival (p = 0.01, HR 0.42(0.21–0.84)), disease-free survival (p = 0.007, HR 0.23(0.08–0.67) and local recurrence-free survival (p = 0.02, HR 0.30(0.11–0.84)). In conclusion, we found that expression of PcG proteins and H3K27me3 showed prognostic value in our study cohort. Better stratification of patients was obtained by combining the expression data of the investigated biomarkers as compared to the individual markers, underlining the importance of investigating multiple markers simultaneously. Public Library of Science 2014-09-22 /pmc/articles/PMC4171510/ /pubmed/25243792 http://dx.doi.org/10.1371/journal.pone.0108265 Text en © 2014 Benard 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Benard, Anne Goossens-Beumer, Inès J. van Hoesel, Anneke Q. Horati, Hamed Putter, Hein Zeestraten, Eliane C. M. van de Velde, Cornelis J. H. Kuppen, Peter J. K.
spellingShingle	Benard, Anne Goossens-Beumer, Inès J. van Hoesel, Anneke Q. Horati, Hamed Putter, Hein Zeestraten, Eliane C. M. van de Velde, Cornelis J. H. Kuppen, Peter J. K. Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
author_facet	Benard, Anne Goossens-Beumer, Inès J. van Hoesel, Anneke Q. Horati, Hamed Putter, Hein Zeestraten, Eliane C. M. van de Velde, Cornelis J. H. Kuppen, Peter J. K.
author_sort	Benard, Anne
title	Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
title_short	Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
title_full	Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
title_fullStr	Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
title_full_unstemmed	Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer
title_sort	prognostic value of polycomb proteins ezh2, bmi1 and suz12 and histone modification h3k27me3 in colorectal cancer
description	Numerous changes in epigenetic mechanisms have been described in various types of tumors. In search for new biomarkers, we investigated the expression of Polycomb-group (PcG) proteins EZH2, BMI1 and SUZ12 and associated histone modification H3K27me3 in colorectal cancer. Nuclear expression of PcG proteins and histone modification H3K27me3 were immunohistochemically (IHC) stained on a tissue microarray (TMA), including 247 tumor tissues and 47 normal tissues, and scored using the semi-automated Ariol system. Tumor tissues showed higher expression of EZH2 (p = 0.05) and H3K27me3 (p<0.001) as compared to their normal counterparts. Combined marker trend analyses indicated that an increase in the number of markers showing high expression was associated with better prognosis. High expression of all four markers in the combined marker analyses was correlated with the best patient survival and the longest recurrence-free survival, with overall survival (p = 0.01, HR 0.42(0.21–0.84)), disease-free survival (p = 0.007, HR 0.23(0.08–0.67) and local recurrence-free survival (p = 0.02, HR 0.30(0.11–0.84)). In conclusion, we found that expression of PcG proteins and H3K27me3 showed prognostic value in our study cohort. Better stratification of patients was obtained by combining the expression data of the investigated biomarkers as compared to the individual markers, underlining the importance of investigating multiple markers simultaneously.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171510/
_version_	1613136063710101504

Prognostic Value of Polycomb Proteins EZH2, BMI1 and SUZ12 and Histone Modification H3K27me3 in Colorectal Cancer

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