Abstract
The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.
Highlights
Gastric cancer is the fourth most common malignancy in the world, the second leading cause of cancer death in men, and the fourth among women according to 2007 statistical data, the worldwide incidence and mortality of gastric cancer have significantly decreased recently
Multivariate Cox regression analysis showed that H3K27me3 and enhancer of zeste homolog 2 (EZH2) expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival
These proteins in gastric cancer and the corresponding adjacent data indicate that both EZH2 and H3K27me3 proteins normal tissues were overexpressed in gastric cancer tissues compared
Summary
Gastric cancer is the fourth most common malignancy in the world, the second leading cause of cancer death in men, and the fourth among women according to 2007 statistical data (www.cancer.org; Global Cancer Facts & Figures 2007), the worldwide incidence and mortality of gastric cancer have significantly decreased recently. The development of biomarkers to predict patient survival and treatment response is necessary to improve the quality of life for patients. Several proteins (such as TGFα, EGFR, and CDC25B) have been identified as markers of gastric cancer (Yasui et al, 2001). These genes are associated with gastric cancer development and progression, which are a multi-step process and a result of the accumulation of various oncogene activations and tumor suppressor gene inactivation (Yasui et al, 2000)
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