title: High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients.
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 < 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.
authors.affiliation: Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Hou
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pei
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lin
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2