Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers

Yongkun Wei, Weiya Xia, Zhihong Zhang, Jinsong Liu, Huamin Wang, Nazmi V. Adsay, Constance Albarracin, Dihua Yu, James L. Abbruzzese, Gordon B. Mills, Robert C. Bast, Gabriel N. Hortobagyi, Mien Chie Hung

    Research output: Contribution to journalArticle

    196 Scopus citations

    Abstract

    Methylation of lysine 27 on histone H3 (H3K27) by the EZH2 complex is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis in both breast and prostate cancers. However, the status of H3K27 methylation and its clinical implication in cancer patients have not been reported. We thus examined trimethylation of H3K27 (H3K27me3) by immunohistochemistry and its association with clinical variables and prognosis in breast, ovanan, and pancreatic cancers. We found that H3K27me3 expression was significantly lower in breast, ovarian and pancreatic cancers than in normal tissues (62% in breast cancer vs. 88% in normal breast tissue, P = 0.001; 38.4% in ovarian cancer vs. 83.3% in normal ovarian tissue, P < 0.05; and 26% in pancreatic cancer vs. 89% in normal pancreatic tissue, P < 0.001). H3K27me3 expression showed significant prognostic impact in breast, ovarian and pancreatic cancers in univariate survival analyses. In all three cancer types, patients with low expression of H3K27me3 had significantly shorter overall survival time when compared with those with high H3K27me3 expression. In a multivariate model, H3K27me3 expression was an independent prognostic value for overall survival in all three cancer types. These results suggest that H3K27me3 expression is a prognostic indicator for clinical outcome in patients with breast, ovarian, and pancreatic cancers.

    Original languageEnglish (US)
    Pages (from-to)701-706
    Number of pages6
    JournalMolecular Carcinogenesis
    Volume47
    Issue number9
    DOIs
    StatePublished - Sep 2008

    Keywords

    • Cancer
    • Histone modification
    • Prognosis

    ASJC Scopus subject areas

    • Molecular Biology
    • Cancer Research

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  • Cite this

    Wei, Y., Xia, W., Zhang, Z., Liu, J., Wang, H., Adsay, N. V., Albarracin, C., Yu, D., Abbruzzese, J. L., Mills, G. B., Bast, R. C., Hortobagyi, G. N., & Hung, M. C. (2008). Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Molecular Carcinogenesis, 47(9), 701-706. https://doi.org/10.1002/mc.20413