@article{oai:nagasaki-u.repo.nii.ac.jp:00005129,
 author = {Chen, Xiaohui and Song, Ning and Matsumoto, Keitaro and Nanashima, Atsushi and Nagayasu, Takeshi and Hayashi, Tomayoshi and Ying, Mingang and Endo, Daisuke and Wu, Zhiren and Koji, Takehiko},
 issue = {5},
 journal = {International Journal of Oncology},
 month = {Nov},
 note = {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., International Journal of Oncology, 43(5), pp.1467-1480; 2013},
 pages = {1467--1480},
 title = {High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer},
 volume = {43},
 year = {2013}
}