Discovery and validation of methylated-differentially expressed genes inHelicobacter pylori-induced gastric cancer
Discovery and validation of methylated-differentially expressed genes inHelicobacter pylori-induced gastric cancer
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幽门螺杆菌诱导的胃癌甲基化差异表达基因的发现和验证
DOI：
10.1038/s41417-019-0125-7
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发表时间：
2020-06-01
影响因子：
6.4
通讯作者：
Wang, Yunshan
中科院分区：
文献类型：
--
作者：
Liu, Duanrui;Ma, Xiaoli;Wang, Yunshan
DNA甲基化在幽门螺杆菌（H. pylori）诱导的胃癌（GC）的过程和发展。本研究的目的是寻找基因组规模的表观遗传修饰，以研究H。幽门螺杆菌诱导的胃癌，并找到与生存和预后相关的因素和强大的签名。本研究对基因表达文库（GEO）中的DNA甲基化和基因表达谱进行了综合分析，以确定差异表达基因（DEG）和差异甲基化基因（DMG）。对筛选出的基因进行功能富集分析，构建蛋白质-蛋白质相互作用网络。TCGA DNA甲基化数据库和55 H. GEO RNA测序的幽门螺杆菌感染的GC病例（GSE 62254）用于枢纽基因的预后价值验证。最后，通过一系列的生物信息学分析，确定了一个与血吸虫病相关的风险特征。幽门螺杆菌引起的胃癌患者。共鉴定出161个DMG。通路分析显示所有MDEG主要与Ras信号通路、肾癌、丝裂原活化蛋白激酶信号通路相关。筛选出CACNB 2、GNB 4、GRIN 2A、MEF 2C和PREX 1等5个中枢基因作为H.幽门螺杆菌引起的胃癌患者。构建了双基因（CACNB 2和MEF 2C）风险标记，用于预测H.幽门螺杆菌引起的胃癌患者。我们的研究提示了H. pylori诱导胃癌的生物信息学分析，为阐明H.幽门螺杆菌诱导的GC。Hub基因可能作为异常甲基化的生物标志物用于H.幽门螺杆菌诱导的GC。
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.