文章：

幽门螺杆菌诱导胃癌中甲基化差异表达基因的发现和验证

Discovery and validation of methylated-differentially expressed genes in Helicobacter pylori-induced gastric cancer 

原文发布日期：2019-07-16 

英文摘要：

DNA methylation has an important role in Helicobacter pylori (H. pylori)-induced gastric cancer (GC) processes and development. The aim of this study was to search genome-scale epigenetic modifications for studying pathogenesis of H. pylori-induced GC, and to find factors and powerful signature related to survival and prognosis. In this study, we conducted a comprehensive analysis of DNA methylation and gene expression profiles in the Gene Expression Omnibus (GEO), to identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs). Functional enrichment analysis of the screened genes was performed, and a protein–protein interaction network was constructed. The TCGA DNA methylation databases and 55 H. pylori-infected GC cases of GEO RNA sequencing (GSE62254) were utilized for prognostic value validation of hub genes. Finally, a prognosis-related risk signature was identified by a series of bioinformatics analysis for H. pylori-induced GC patients. Totally, 161 DMGs were identified. Pathway analysis showed that all MDEGs mainly associated with Ras signaling pathway, renal cell carcinoma, mitogen-activated protein kinase signaling pathway. Five hub genes including CACNB2, GNB4, GRIN2A, MEF2C, and PREX1 were screened as independent prognostic factors in H. pylori-induced GC patients. Two-gene (CACNB2 and MEF2C) risk signature was constructed for predicting the overall survival of H. pylori-induced GC patients. Our study indicated possible MDEGs and pathways in H. pylori-induced GC by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of H. pylori-induced GC. Hub genes might serve as aberrantly methylation-based biomarkers for clinical diagnostic and prognostic evaluation of H. pylori-induced GC. 

摘要翻译： 

DNA甲基化在幽门螺杆菌（H. pylori）诱导的胃癌（GC）发生发展过程中具有重要作用。本研究旨在通过全基因组尺度的表观遗传修饰探究幽门螺杆菌诱导胃癌的发病机制，并寻找与生存和预后相关的因素及有效标志物。我们通过对基因表达综合数据库（GEO）中DNA甲基化和基因表达谱进行全面分析，识别出差异表达基因（DEGs）和差异甲基化基因（DMGs）。对筛选基因进行功能富集分析并构建蛋白质-蛋白质相互作用网络，利用TCGA DNA甲基化数据库及GEO中55例幽门螺杆菌感染胃癌病例的RNA测序数据（GSE62254）验证核心基因的预后价值。最终通过系列生物信息学分析确定了幽门螺杆菌诱导胃癌患者的预后相关风险标志。共鉴定出161个差异甲基化基因，通路分析显示所有差异甲基化表达基因主要与Ras信号通路、肾细胞癌、丝裂原活化蛋白激酶信号通路相关。筛选出CACNB2、GNB4、GRIN2A、MEF2C和PREX1五个核心基因作为幽门螺杆菌诱导胃癌患者的独立预后因素，并构建了基于CACNB2和MEF2C的双基因风险标志用于预测患者总生存期。本研究通过生物信息学分析揭示了幽门螺杆菌诱导胃癌中潜在的差异甲基化表达基因及通路，为阐明其发病机制提供了新见解。核心基因可能作为基于异常甲基化的生物标志物，用于幽门螺杆菌诱导胃癌的临床诊断和预后评估。

原文链接：

Discovery and validation of methylated-differentially expressed genes in Helicobacter pylori-induced gastric cancer