摘要
背景:EZH2是表观遗传调控因子PcG蛋白的核心成分,可通过催化组蛋白H3氨基末端第27位赖氨酸发生三甲基化而抑制靶基因表达。研究发现EZH2在前列腺癌、乳腺癌、胃癌等恶性肿瘤组织中表达增高,并与肿瘤进展和预后差相关。目的:探讨EZH2在胃癌发生、发展中的作用和临床意义及其与细胞增殖的关系。方法:应用免疫组化技术检测32例正常胃黏膜、34例慢性非萎缩性胃炎、33例慢性萎缩性胃炎、40例异型增生和69例胃癌组织中EZH2、Ki-67的表达情况,分析EZH2与Ki-67和胃癌临床病理特征之间的相关性。结果:EZH2在正常胃黏膜和慢性胃炎组织中主要表达于腺颈部,在正常胃黏膜、慢性非萎缩性胃炎、慢性萎缩性胃炎和异型增生组织中,其表达水平逐渐增高(P〈O.05),异型增生与胃癌组织间则无明屁差异(P=0.678)。各病变组织中,EZH2与Ki-67的表达水平均呈正相关(P〈0.01),所有组织中EZH2总体表达水平显著高于Ki-67(P〈0.01)。胃癌组织中EZH2的表达水平与肿瘤大小、浸润深度、淋巴结转移和TNM分期相关(P〈0.05)。结论:EZH2过表达是胃癌发生过程中的早期分子事件,其可能通过促进胃腺上皮增殖参与了胃癌的发生、发展过程。
Background: EZH2, the core component of epigenetic regulator polycomb group proteins, can suppress the expression of target genes by catalyzing the trimethylation of histone H3 lysine 27. It is overexpressed in prostate cancer, breast cancer, gastric cancer and some other malignancies, and its expression level is usually correlated with tumor progression and poor prognosis. Aims: To investigate the role and clinical significance of EZH2 in the carcinogenesis and progression of gastric cancer, and its relationship with cell proliferation. Methods: Immunohistochemical analysis was used to detect the expressions of EZH2 and Ki-67 in specimens of 32 normal gastric mucosa, 34 chronic non-atrophic gastritis, 33 chronic atrophic gastritis, 40 dysplasia and 69 gastric cancer. The relevance of EZH2 with Ki-67 and the clinicopathologic characteristics of gastric cancer were analyzed. Results: In normal mucosa and chronic gastritis, the expression of EZH2 was mainly distributed in the neck of the gland. The expression level increased stepwisely in the specimens of normal gastric mucosa, chronic non-atrophic gastritis, chronic atrophic gastritis and dysplasia (P〈0,05), while no significant difference was found between dysplasia and gastric cancer (P=0.678). Among groups of gastritis, dysplasia and gastric cancer, positive correlation was seen between the expressions of EZH2 and Ki-67 (P〈0.01, respectively), and the overall expression of EZH2 was higher than that of Ki-67 in all specimens (P〈0.01). The expression of EZH2 was correlated with the tumor size, depth of invasion, lymph node metastasis and TNM stage of gastric cancer (P〈0.05). Conclusions: Overexpression of EZH2 is an early molecular event of gastric carcinogenesis. EZH2 might be involved in the carcinogenesis and progression of gastric cancer lay promoting proliferation of glandular epithelial cells.
出处
《胃肠病学》
2010年第6期339-343,共5页
Chinese Journal of Gastroenterology
基金
上海市重点学科建设项目资助(Y0205)