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H. Tomayoshi
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-124 - High Expression of Trimethylated Histone H3 at Lysine 27 Predicts Better Prognosis in Non-Small Cell Lung Cancer (ID 486)
09:30 - 09:30 | Author(s): H. Tomayoshi
- Abstract
Background:
Lung cancer is still the leading cause of cancer death in both sexes throughout the world. The alterations in epigenomes such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. It has been reported that DNA methylation level and global histone modification patterns may be possible predictors of cancer recurrence and prognosis in a large variety of cancer entities. One such repressive modification, the trimethylation of lysine 27 on histone H3 (H3K27me3), seemed to be an epigenetic label mediating gene silencing; and a mark for de novo DNA methylation in cancer cells by recruitment of DNA methyltransferase (DNMTs) , contributing to tumor progression through suppression of a certain gene expression. In fact, many recent studies have revealed that H3K27me3 may be involved in the characterization of various types of human cancers, excluding NSCLC. Interestingly, reports of H3K27me3 levels in different cancer samples are somewhat contradictory. It’s demonstrated that low H3K27me3 levels predicted poor outcome in breast, ovarian and pancreatic cancers while high levels predicted poor outcome in hepatocellular carcinoma and esophageal squamous cell carcinoma. Moreover, H3K27 methylation is catalyzed by its specific methyltransferase, EZH2. Overexpression of EZH2 was also found in a variety of cancers, resulting in worse clinical outcome. Although many reports on the role of H3K27me3 in carcinogenesis were available, its carcinogenic role in NSCLC and how it interacts with EZH2 and DNA methylation remain unclear.
Methods:
Expressions 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 were testified by western blotting. The optimal cut-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.
Results:
Figure 1 Enhanced trimethylation of H3K27me3 was correlated with longer OS and better prognosis (P<0.05). 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)
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.
