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High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer


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Title: High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer
Authors: Chen, Xiaohui / Song, Ning / Matsumoto, Keitaro / Nanashima, Atsushi / Nagayasu, Takeshi / Hayashi, Tomayoshi / Ying, Mingang / Endo, Daisuke / Wu, Zhiren / Koji, Takehiko
Issue Date: Nov-2013
Publisher: Spandidos Publications
Citation: International Journal of Oncology, 43(5), pp.1467-1480; 2013
Abstract: Epigenetic parameters such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. Global histone modification patterns have been implicated as possible predictors of cancer recurrence and prognoses in a great variety of tumor entities. Our study was designed to evaluate the association among trimethylated histone H3 at lysine 27 (H3K27me3), clinicopathological variables and outcome in early-stage non-small cell lung cancer (NSCLC). The expression of H3K27me3 and its methyltransferase, enhancer of zeste homolog 2 (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients (n=42). In addition, the specificity of antibody for H3K27me3 was tested by western blot analysis. The optimal cut-off point of H3K27me3 expression for prognosis was determined by the X-tile program. The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests. As a result, enhanced trimethylation of H3K27me3 was correlated with longer overall survival (OS) and better prognosis (P<0.05). Moreover, both univariate and multivariate analyses indicated that H3K27me3 level was a significant and independent predictor of better survival (hazard ratio, 0.187; 95% confidence interval, 0.066-0.531, P=0.002). Furthermore, H3K27me3 expression was positively correlated with DNA methylation level at CCGG sites while reversely related to EZH2 expression (P<0.05). In conclusion, H3K27me3 level defines unrecognized subgroups of NSCLC patients with distinct epigenetic phenotype and clinical outcome, and can probably be used as a novel predictor for better prognosis in NSCLC patients.
Keywords: DNA methylation / Enhancer of zeste homolog 2 / Epigenetics / Non-small cell lung cancer / Trimethylated histone H3 at lysine 27
URI: http://hdl.handle.net/10069/34168
ISSN: 10196439
DOI: 10.3892/ijo.2013.2062
Rights: © Spandidos Publications 2013. All rights reserved.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34168

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