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Article: High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients
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TitleHigh expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients
 
AuthorsCai, MY1 1
Hou, JH1 1
Rao, HL1 1
Luo, RZ1 1
Li, M1 1
Pei, XQ1
Lin, MC1 2
Guan, XY1
Kung, HF1 2
Zeng, YX1
Xie, D1
 
Issue Date2011
 
PublisherThe Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.org
 
CitationMolecular Medicine, 2011, v. 17 n. 1-2, p. 12-20 [How to Cite?]
DOI: http://dx.doi.org/10.2119/molmed.2010.00103
 
AbstractIt has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression dynamics of H3K27me3 and its clinicopathological/prognostic significance in hepatocellular carcinoma (HCC) are unclear. In this study, immunohistochemical analysis (IHC) was used to examine protein expression of H3K27me3 in HCC tissues from two independent cohorts and corresponding nontumorous hepatocellular tissues by tissue microarray. The optimal cutpoint of H3K27me3 expression was assessed by the X-tile program. Our results showed that the cutpoint for high expression of H3K27me3 in HCCs was determined when more than 70% of the tumor cells showed positive staining. High expression of H3K27me3 was observed in 134 of 212 (63.2%) and 76 of 126 (60.4%) of HCCs in the testing and validation cohorts, respectively. Correlation analysis demonstrated that high expression of H3K27me3 in HCCs was significantly correlated with large tumor size, multiplicity, poor differentiation, advanced clinical stage and vascular invasion (P < 0.05). In addition, high expression of H3K27me3 in HCC patients was associated closely with shortened survival time, independent of serum α-fetoprotein levels, tumor size and multiplicity, clinical stage, vascular invasion and relapse as evidenced by univariate and multivariate analysis in both cohorts (P < 0.05). In different subsets of HCC patients, H3K27me3 expression was also a prognostic indicator in patients with stage II tumors (P < 0.05). Thus, these findings provide evidence that a high expression of H3K27me3, as detected by IHC, correlates closely with vascular invasion of HCCs and is an independent molecular marker for poor prognosis in patients with HCC. ©2011 The Feinstein Institute for Medical Research.
 
ISSN1076-1551
2012 Impact Factor: 4.469
2012 SCImago Journal Rankings: 1.572
 
DOIhttp://dx.doi.org/10.2119/molmed.2010.00103
 
PubMed Central IDPMC3022987
 
ISI Accession Number IDWOS:000286708100004
Funding AgencyGrant Number
973 Project of China2010CB529401
2010CB912803
Foundation of Guangzhou Science and Technology Bureau, China2005Z1-E0131
863 Project of China2007AA021901
Funding Information:

This work was supported by the 973 Project of China (2010CB529401 and 2010CB912803), the Foundation of Guangzhou Science and Technology Bureau, China (2005Z1-E0131) and the 863 Project of China (2007AA021901).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCai, MY
 
dc.contributor.authorHou, JH
 
dc.contributor.authorRao, HL
 
dc.contributor.authorLuo, RZ
 
dc.contributor.authorLi, M
 
dc.contributor.authorPei, XQ
 
dc.contributor.authorLin, MC
 
dc.contributor.authorGuan, XY
 
dc.contributor.authorKung, HF
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorXie, D
 
dc.date.accessioned2011-08-26T14:22:11Z
 
dc.date.available2011-08-26T14:22:11Z
 
dc.date.issued2011
 
dc.description.abstractIt has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression dynamics of H3K27me3 and its clinicopathological/prognostic significance in hepatocellular carcinoma (HCC) are unclear. In this study, immunohistochemical analysis (IHC) was used to examine protein expression of H3K27me3 in HCC tissues from two independent cohorts and corresponding nontumorous hepatocellular tissues by tissue microarray. The optimal cutpoint of H3K27me3 expression was assessed by the X-tile program. Our results showed that the cutpoint for high expression of H3K27me3 in HCCs was determined when more than 70% of the tumor cells showed positive staining. High expression of H3K27me3 was observed in 134 of 212 (63.2%) and 76 of 126 (60.4%) of HCCs in the testing and validation cohorts, respectively. Correlation analysis demonstrated that high expression of H3K27me3 in HCCs was significantly correlated with large tumor size, multiplicity, poor differentiation, advanced clinical stage and vascular invasion (P < 0.05). In addition, high expression of H3K27me3 in HCC patients was associated closely with shortened survival time, independent of serum α-fetoprotein levels, tumor size and multiplicity, clinical stage, vascular invasion and relapse as evidenced by univariate and multivariate analysis in both cohorts (P < 0.05). In different subsets of HCC patients, H3K27me3 expression was also a prognostic indicator in patients with stage II tumors (P < 0.05). Thus, these findings provide evidence that a high expression of H3K27me3, as detected by IHC, correlates closely with vascular invasion of HCCs and is an independent molecular marker for poor prognosis in patients with HCC. ©2011 The Feinstein Institute for Medical Research.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationMolecular Medicine, 2011, v. 17 n. 1-2, p. 12-20 [How to Cite?]
DOI: http://dx.doi.org/10.2119/molmed.2010.00103
 
dc.identifier.doihttp://dx.doi.org/10.2119/molmed.2010.00103
 
dc.identifier.epage20
 
dc.identifier.hkuros190865
 
dc.identifier.isiWOS:000286708100004
Funding AgencyGrant Number
973 Project of China2010CB529401
2010CB912803
Foundation of Guangzhou Science and Technology Bureau, China2005Z1-E0131
863 Project of China2007AA021901
Funding Information:

This work was supported by the 973 Project of China (2010CB529401 and 2010CB912803), the Foundation of Guangzhou Science and Technology Bureau, China (2005Z1-E0131) and the 863 Project of China (2007AA021901).

 
dc.identifier.issn1076-1551
2012 Impact Factor: 4.469
2012 SCImago Journal Rankings: 1.572
 
dc.identifier.issue1-2
 
dc.identifier.pmcidPMC3022987
 
dc.identifier.pmid20844838
 
dc.identifier.scopuseid_2-s2.0-78651506355
 
dc.identifier.spage12
 
dc.identifier.urihttp://hdl.handle.net/10722/137269
 
dc.identifier.volume17
 
dc.languageeng
 
dc.publisherThe Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofMolecular Medicine
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCarcinoma, Hepatocellular - blood supply - diagnosis - genetics - pathology
 
dc.subject.meshGene Expression Regulation, Neoplastic
 
dc.subject.meshHistones - genetics - metabolism
 
dc.subject.meshLiver Neoplasms - blood supply - diagnosis - genetics - pathology
 
dc.subject.meshTumor Markers, Biological
 
dc.titleHigh expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients
 
dc.typeArticle
 
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<description.abstract>It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression dynamics of H3K27me3 and its clinicopathological/prognostic significance in hepatocellular carcinoma (HCC) are unclear. In this study, immunohistochemical analysis (IHC) was used to examine protein expression of H3K27me3 in HCC tissues from two independent cohorts and corresponding nontumorous hepatocellular tissues by tissue microarray. The optimal cutpoint of H3K27me3 expression was assessed by the X-tile program. Our results showed that the cutpoint for high expression of H3K27me3 in HCCs was determined when more than 70% of the tumor cells showed positive staining. High expression of H3K27me3 was observed in 134 of 212 (63.2%) and 76 of 126 (60.4%) of HCCs in the testing and validation cohorts, respectively. Correlation analysis demonstrated that high expression of H3K27me3 in HCCs was significantly correlated with large tumor size, multiplicity, poor differentiation, advanced clinical stage and vascular invasion (P &lt; 0.05). In addition, high expression of H3K27me3 in HCC patients was associated closely with shortened survival time, independent of serum &#945;-fetoprotein levels, tumor size and multiplicity, clinical stage, vascular invasion and relapse as evidenced by univariate and multivariate analysis in both cohorts (P &lt; 0.05). In different subsets of HCC patients, H3K27me3 expression was also a prognostic indicator in patients with stage II tumors (P &lt; 0.05). Thus, these findings provide evidence that a high expression of H3K27me3, as detected by IHC, correlates closely with vascular invasion of HCCs and is an independent molecular marker for poor prognosis in patients with HCC. &#169;2011 The Feinstein Institute for Medical Research.</description.abstract>
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Author Affiliations
  1. Sun Yat-Sen University Cancer Center
  2. Chinese University of Hong Kong