Emerging role of linker histone variant H1x as a biomarker with prognostic value in astrocytic gliomas. A multivariate analysis including trimethylation of H3K9 and H4K20

Although epigenetic alterations play an essential role in gliomagenesis, the relevance of aberrant histone modifications and the respective enzymes has not been clarified. Experimental data implicates histone H3 lysine (K) methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linke...

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Published in:PloS one 2015-01, Vol.10 (1), p.e0115101
Main Authors: Sepsa, Athanasia, Levidou, Georgia, Gargalionis, Antonis, Adamopoulos, Christos, Spyropoulou, Anastasia, Dalagiorgou, Georgia, Thymara, Irene, Boviatsis, Efstathios, Themistocleous, Marios S, Petraki, Kalliopi, Vrettakos, George, Samaras, Vassilis, Zisakis, Athanassios, Patsouris, Efstratios, Piperi, Christina, Korkolopoulou, Penelope
Format: Article
Language:English
Subjects:
Aberration
Adult
Aged
Aged, 80 and over
Analysis
Bioindicators
Biomarkers
Biomarkers, Tumor
Brain
Brain - metabolism
Brain cancer
Brain tumors
Breast cancer
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement
Cell Proliferation
Chemistry
Chromatin
Cohort Studies
Deoxyribonucleic acid
Deregulation
DNA
DNA methylation
Enzymes
Epigenetic inheritance
Epigenetics
Female
Gene expression
Glioblastoma - diagnosis
Glioblastoma - metabolism
Glioblastoma - mortality
Glioblastoma - therapy
Glioma
Gliomas
Histone H3
Histones
Histones - metabolism
Humans
Immunoblotting
Immunohistochemistry
Immunoreactivity
Kaplan-Meier Estimate
Lysine
Male
Mammals
Medical prognosis
Medical schools
Methylation
Middle Aged
Multivariate analysis
Neoplasm Grading
Neurosurgery
Pathogenesis
Pathology
Phosphorylation
Prognosis
Proteins
Survival
Tumors
Young Adult
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cited_by cdi_FETCH-LOGICAL-c692t-58cbce38d8514e87d188f23c7c8ecedd8c4633245d42fafdbd73b7b87b3626ec3
cites cdi_FETCH-LOGICAL-c692t-58cbce38d8514e87d188f23c7c8ecedd8c4633245d42fafdbd73b7b87b3626ec3
container_end_page
container_issue 1
container_start_page e0115101
container_title PloS one
container_volume 10
creator Sepsa, Athanasia
Levidou, Georgia
Gargalionis, Antonis
Adamopoulos, Christos
Spyropoulou, Anastasia
Dalagiorgou, Georgia
Thymara, Irene
Boviatsis, Efstathios
Themistocleous, Marios S
Petraki, Kalliopi
Vrettakos, George
Samaras, Vassilis
Zisakis, Athanassios
Patsouris, Efstratios
Piperi, Christina
Korkolopoulou, Penelope
description Although epigenetic alterations play an essential role in gliomagenesis, the relevance of aberrant histone modifications and the respective enzymes has not been clarified. Experimental data implicates histone H3 lysine (K) methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linker histone variant H1.0 and H4K20me3 reportedly affect prognosis. We investigated the expression of H3K9me3 and its methyltransferases along with H4K20me3 and H1x in 101 astrocytic tumors with regard to clinicopathological characteristics and survival. The effect of SUV39H1 inhibition by chaetocin on the proliferation, colony formation and migration of T98G cells was also examined. SETDB1 and cytoplasmic SUV39H1 levels increased from normal brain through low-grade to high-grade tumors, nuclear SUV39H1 correlating inversely with grade. H3K9me3 immunoreactivity was higher in normal brain showing no association with grade, whereas H1x and H4K20me3 expression was higher in grade 2 than in normal brain or high grades. These expression patterns of H1x, H4K20me3 and H3K9me3 were verified by Western immunoblotting. Chaetocin treatment significantly reduced proliferation, clonogenic potential and migratory ability of T98G cells. H1x was an independent favorable prognosticator in glioblastomas, this effect being validated in an independent set of 66 patients. Diminished nuclear SUV39H1 expression adversely affected survival in univariate analysis. In conclusion, H4K20me3 and H3K9 methyltransferases are differentially implicated in astroglial tumor progression. Deregulation of H1x emerges as a prognostic biomarker.
doi_str_mv 10.1371/journal.pone.0115101
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Deregulation of H1x emerges as a prognostic biomarker.</description><subject>Aberration</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Bioindicators</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Breast cancer</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Chemistry</subject><subject>Chromatin</subject><subject>Cohort Studies</subject><subject>Deoxyribonucleic acid</subject><subject>Deregulation</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Enzymes</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glioblastoma - 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest advanced technologies &amp; aerospace journals</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sepsa, Athanasia</au><au>Levidou, Georgia</au><au>Gargalionis, Antonis</au><au>Adamopoulos, Christos</au><au>Spyropoulou, Anastasia</au><au>Dalagiorgou, Georgia</au><au>Thymara, Irene</au><au>Boviatsis, Efstathios</au><au>Themistocleous, Marios S</au><au>Petraki, Kalliopi</au><au>Vrettakos, George</au><au>Samaras, Vassilis</au><au>Zisakis, Athanassios</au><au>Patsouris, Efstratios</au><au>Piperi, Christina</au><au>Korkolopoulou, Penelope</au><au>Zhu, Wei-Guo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emerging role of linker histone variant H1x as a biomarker with prognostic value in astrocytic gliomas. A multivariate analysis including trimethylation of H3K9 and H4K20</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-01-20</date><risdate>2015</risdate><volume>10</volume><issue>1</issue><spage>e0115101</spage><pages>e0115101-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Although epigenetic alterations play an essential role in gliomagenesis, the relevance of aberrant histone modifications and the respective enzymes has not been clarified. Experimental data implicates histone H3 lysine (K) methyltransferases SETDB1 and SUV39H1 into glioma pathobiology, whereas linker histone variant H1.0 and H4K20me3 reportedly affect prognosis. We investigated the expression of H3K9me3 and its methyltransferases along with H4K20me3 and H1x in 101 astrocytic tumors with regard to clinicopathological characteristics and survival. The effect of SUV39H1 inhibition by chaetocin on the proliferation, colony formation and migration of T98G cells was also examined. SETDB1 and cytoplasmic SUV39H1 levels increased from normal brain through low-grade to high-grade tumors, nuclear SUV39H1 correlating inversely with grade. H3K9me3 immunoreactivity was higher in normal brain showing no association with grade, whereas H1x and H4K20me3 expression was higher in grade 2 than in normal brain or high grades. These expression patterns of H1x, H4K20me3 and H3K9me3 were verified by Western immunoblotting. Chaetocin treatment significantly reduced proliferation, clonogenic potential and migratory ability of T98G cells. H1x was an independent favorable prognosticator in glioblastomas, this effect being validated in an independent set of 66 patients. Diminished nuclear SUV39H1 expression adversely affected survival in univariate analysis. In conclusion, H4K20me3 and H3K9 methyltransferases are differentially implicated in astroglial tumor progression. Deregulation of H1x emerges as a prognostic biomarker.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25602259</pmid><doi>10.1371/journal.pone.0115101</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
1932-6203
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subjects Aberration
Adult
Aged
Aged, 80 and over
Analysis
Bioindicators
Biomarkers
Biomarkers, Tumor
Brain
Brain - metabolism
Brain cancer
Brain tumors
Breast cancer
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement
Cell Proliferation
Chemistry
Chromatin
Cohort Studies
Deoxyribonucleic acid
Deregulation
DNA
DNA methylation
Enzymes
Epigenetic inheritance
Epigenetics
Female
Gene expression
Glioblastoma - diagnosis
Glioblastoma - metabolism
Glioblastoma - mortality
Glioblastoma - therapy
Glioma
Gliomas
Histone H3
Histones
Histones - metabolism
Humans
Immunoblotting
Immunohistochemistry
Immunoreactivity
Kaplan-Meier Estimate
Lysine
Male
Mammals
Medical prognosis
Medical schools
Methylation
Middle Aged
Multivariate analysis
Neoplasm Grading
Neurosurgery
Pathogenesis
Pathology
Phosphorylation
Prognosis
Proteins
Survival
Tumors
Young Adult
title Emerging role of linker histone variant H1x as a biomarker with prognostic value in astrocytic gliomas. A multivariate analysis including trimethylation of H3K9 and H4K20
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