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

Chen,Xiaohui; Song,Ning; Matsumoto,Keitaro; Nanashima,Atsushi; Nagayasu,Takeshi; Hayashi,Tomayoshi; Ying,Mingang; Endo,Daisuke; Wu,Zhiren; Koji,Takehiko

doi:10.3892/ijo.2013.2062

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

Authors:
- Xiaohui Chen
- Ning Song
- Keitaro Matsumoto
- Atsushi Nanashima
- Takeshi Nagayasu
- Tomayoshi Hayashi
- Mingang Ying
- Daisuke Endo
- Zhiren Wu
- Takehiko Koji
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Affiliations: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan, Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan, Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan, Division of Oncological Surgery, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Fujian, P.R. China
Published online on: August 20, 2013 https://doi.org/10.3892/ijo.2013.2062
Pages: 1467-1480

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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.

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