DNA甲基化转移酶在胃癌中的表达及其临床意义

doi:10.6040/j.issn.1671-7554.0.2021.0055

摘要/Abstract

摘要： 目的探讨胃癌中DNA甲基化转移酶(DNMT1、DNMT3A、DNMT3B)表达的临床意义与预后的相关性。方法运用TCGA和GEO数据库分析DNA甲基化转移酶在胃癌和正常组织中的表达差异; 运用生存期分析软件Kaplan-Meier plotter分析DNA甲基化转移酶对胃癌患者预后的影响;下载TCGA和GEO数据库中的原始数据,分析DNA甲基化转移酶与临床病理参数之间的关系;采用基因富集分析(GSEA)结合蛋白互作网络进行DNMT3B的生物学功能研究。TCGA数据库分析DNMT3B升高促进胃癌进展的具体机制。结果在胃癌组织中3种DNA甲基化转移酶的表达均高于癌旁正常组织;生存分析结果发现,DNMT3A、DNMT3B高表达的患者总生存期较短;DNMT3B表达与组织学分型相关,在肠型胃癌中表达较高;幽门螺旋杆菌感染可促进DNMT3B表达;DNMT3B可能通过影响BUB1、HDAC2的甲基化促进胃癌的进展。结论 DNA甲基化转移酶在胃癌组织中高表达,DNMT3B是胃癌患者的一个预后指标,可能成为临床诊治胃癌的生物标志物。

关键词: DNA甲基化转移酶, 胃癌, 预后, TCGA数据库, GEO数据库

Abstract: Objective To investigate the expressions of DNA methyltransferases(DNMT1, DNMT3A, DNMT3B)in gastric cancer and its correlation with the clinicopathological parameters and prognosis of gastric cancer. Methods Based on TCGA and GEO data, the differences in DNA methyltransferases expressions were compared between gastric cancer and adjacent normal tissues; the effects of DNA methyltransferases on the prognosis of patients with gastric cancer were analyzed with Kaplan-Meier plotter; the relationship between DNA methyltransferases and clinicopathological parameters was analyzed; the biological function of DNMT3B was explored with gene enrichment analysis(GSEA)binding protein interaction network. The mechanism of DNMT3B elevation in the progression of gastric cancer was also analyzed. Results The expressions of three DNA methyltransferases in gastric cancer tissues were higher than those in adjacent normal tissues; survival analysis showed that patients with high expressions of DNMT3A and DNMT3B had shorter overall survival; DNMT3B expression was related to the histological type, and was high in intestinal type gastric cancer; Helicobacter pylori infection promoted the expression of DNMT3B; DNMT3B promoted the progression of gastric cancer by affecting the methylation of BUB1 and HDAC2. Conclusion DNA methyltransferases are highly expressed in gastric cancer. DNMT3B is a prognostic indicator of gastric cancer and may be a biomarker for the clinical diagnosis and treatment of gastric cancer.

Key words: DNA methyltransferase, Gastric cancer, Prognosis, TCGA database, GEO database

中图分类号:

R735.2

褚晏,刘端瑞,朱文帅,樊荣,马晓丽,汪运山,郏雁飞. DNA甲基化转移酶在胃癌中的表达及其临床意义[J]. 山东大学学报 (医学版), 2021, 59(7): 1-9.

CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance[J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.

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