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Article: High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients

TitleHigh expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients
Authors
Issue Date2011
PublisherThe Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.org
Citation
Molecular Medicine, 2011, v. 17 n. 1-2, p. 12-20 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/137269
ISSN
2014 Impact Factor: 4.508
2014 SCImago Journal Rankings: 2.232
PubMed Central ID
ISI Accession Number ID
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).

References

 

DC FieldValueLanguage
dc.contributor.authorCai, MYen_HK
dc.contributor.authorHou, JHen_HK
dc.contributor.authorRao, HLen_HK
dc.contributor.authorLuo, RZen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorPei, XQen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorXie, Den_HK
dc.date.accessioned2011-08-26T14:22:11Z-
dc.date.available2011-08-26T14:22:11Z-
dc.date.issued2011en_HK
dc.identifier.citationMolecular Medicine, 2011, v. 17 n. 1-2, p. 12-20en_HK
dc.identifier.issn1076-1551en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137269-
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.en_HK
dc.languageengen_US
dc.publisherThe Feinstein Institute for Medical Research. The Journal's web site is located at http://www.molmed.orgen_HK
dc.relation.ispartofMolecular Medicineen_HK
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 patientsen_HK
dc.typeArticleen_HK
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.2119/molmed.2010.00103en_HK
dc.identifier.pmid20844838-
dc.identifier.pmcidPMC3022987-
dc.identifier.scopuseid_2-s2.0-78651506355en_HK
dc.identifier.hkuros190865en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78651506355&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume17en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage12en_HK
dc.identifier.epage20en_HK
dc.identifier.isiWOS:000286708100004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCai, MY=23388510500en_HK
dc.identifier.scopusauthoridHou, JH=7401966118en_HK
dc.identifier.scopusauthoridRao, HL=35277843000en_HK
dc.identifier.scopusauthoridLuo, RZ=8242905800en_HK
dc.identifier.scopusauthoridLi, M=36802240200en_HK
dc.identifier.scopusauthoridPei, XQ=7102484616en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK

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