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Molecular Medicine

, Volume 17, Issue 1–2, pp 12–20 | Cite as

High Expression of H3K27me3 in Human Hepatocellular Carcinomas Correlates Closely with Vascular Invasion and Predicts Worse Prognosis in Patients

  • Mu-Yan Cai
  • Jing-Hui Hou
  • Hui-Lan Rao
  • Rong-Zhen Luo
  • Mei Li
  • Xiao-Qing Pei
  • Marie C. Lin
  • Xin-Yuan Guan
  • Hsiang-Fu Kung
  • Yi-Xin Zeng
  • Dan Xie
Research Article

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.

Notes

Acknowledgments

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).

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Mu-Yan Cai
    • 1
    • 2
  • Jing-Hui Hou
    • 1
    • 2
  • Hui-Lan Rao
    • 1
    • 2
  • Rong-Zhen Luo
    • 1
    • 2
  • Mei Li
    • 1
    • 2
  • Xiao-Qing Pei
    • 3
  • Marie C. Lin
    • 1
    • 4
  • Xin-Yuan Guan
    • 1
  • Hsiang-Fu Kung
    • 1
    • 4
  • Yi-Xin Zeng
    • 1
  • Dan Xie
    • 1
  1. 1.State Key Laboratory of Oncology in South China, Cancer CenterSun Yat-Sen University No. 651GuangzhouChina
  2. 2.Departments of PathologySun Yat-Sen University Cancer CenterGuangzhouChina
  3. 3.Departments of UltrasoundSun Yat-Sen University Cancer CenterGuangzhouChina
  4. 4.State Key Laboratory of Oncology in South Chinathe Chinese University of Hong KongHong KongChina

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