He Long-Jun, Cai Mu-Yan, Xu Guo-Liang, Li Jian-Jun, Weng Zi-Jin, Xu Da-Zhi, Luo Guang-Yu, Zhu Sen-Lin, Xie Dan
The State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou, China.
Asian Pac J Cancer Prev. 2012;13(7):3173-8. doi: 10.7314/apjcp.2012.13.7.3173.
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.
zeste 同源物 2（EZH2）甲基转移酶和组蛋白 3 赖氨酸 27（H3K27me3）蛋白可抑制基因转录，且在多种人类癌症中均观察到它们的异常表达。本研究参照临床病理特征和患者生存率确定了它们在胃癌组织中的表达水平。我们收集了 117 例胃癌组织及相应的正常组织进行免疫组织化学分析。在胃癌中，EZH2 蛋白阳性率为 82/117（70.1%），H3K27me3 蛋白阳性率为 66/117（56.4%），而正常胃黏膜标本的阳性率分别仅为 5.41%和 7.25%。Kaplan-Meier 生存数据显示，EZH2 高表达患者的平均总生存期和无病生存期分别为 25.2 个月和 20.2 个月，短于 EZH2 低表达患者（40.5 个月和 35.9 个月）。H3K27me3 高表达患者的平均总生存期和无病生存期分别为 23.4 个月和 17.4 个月，短于无 H3K27me3 表达的患者（37.6 个月和 34.5 个月）。EZH2 和 H3K27me3 均表达的患者平均总生存期和无病生存期分别为 18.8 个月和 12.9 个月，短于单独一种蛋白表达的患者（34.7 个月和 31.2 个月）或两者低表达的患者（43.9 个月和 39.9 个月）。多因素 Cox 回归分析表明，H3K27me3 和 EZH2 表达、肿瘤大小分化及临床分期均为预测患者生存的独立预后因素。本研究表明，检测 EZH2 和 H3K27me3 蛋白均可预测胃癌患者的不良生存情况，优于单一蛋白检测。此外，H3K27me3 和 EZH2 蛋白表达可预测淋巴结转移。
