幽门螺杆菌感染与胃癌相关基因的筛选及预后分析

目的 通过分析幽门螺杆菌感染胃黏膜组织和胃癌细胞系后的差异基因变化,并在癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和肿瘤基因芯片(Oncomine)数据库进行验证,探究幽门螺杆菌导致胃癌发生、发展的分子机制。 方法 分析基因表达汇编(Gene Expression Omnibus,GEO)数据库幽门螺杆菌感染相关芯片集GSE5081与GSE70394,绘制维恩图查找幽门螺杆菌感染后共同上调的差异基因。对共同上调的差异基因进行功能富集分析。通过TCGA和Oncomine数据库验证差异基因在胃癌中的表达。利用Kaplan Meier Plotter数据库和GEPIA数据库分析差异基因表达高低与胃癌患者预后是否存在相关性。 结果 通过差异基因筛选和维恩分析,两个芯片集共有21个共同上调差异基因。GO分析发现共同上调差异基因主要富集在对细菌来源分子的反应、趋化因子CXCR受体结合、中性粒细胞趋化作用等相关的基因功能上；KEGG通路主要富集在癌症通路、TNF信号通路、趋化因子信号通路等。STRING以及PPI数据库分析发现21个基因中PRDM1、IL10、NRP1、BIRC3、GNG13、CXCL1、CXCL2、CXCL3、CXCL8基因存在有网络关系,属于关键枢纽基因。通过TCGA和Oncomine数据库筛选及验证,发现在胃癌组织中NRP1、CXCL1、CXCL8 基因明显上调,结果差异有统计学意义(TCGA数据库中,三者P值均小于0.05,Oncomine数据库中,NRP1:t=4.607,P结论 不同的数据库均显示NRP1、CXCL1、CXCL8三个基因与幽门螺杆菌感染相关,同时在胃癌中高表达,并且NRP1的高表达与胃癌的不良预后相关,这些结果为进一步探究幽门螺杆菌导致胃癌发生、发展的分子机制提供了重要基础。

Screening and prognostic analysis of Helicobacter pylori infection and gastric cancer related genes

Objective To explore the molecular mechanisms of H. pylori infection and gastric cancer (GC). Methods Data of GSE5081 and GSE70394 downloaded from GEO database were used for analyzing the changes in gene expression between H. pylori infected or uninfected gastric mucosa and GC cell lines. The co upregulated genes were recruited through Venn diagram. The analysis of upregulated genes were performed through GO and KEGG pathway analysis. Oncomine and TCGA database were used for investigating the expression of different genes in GC. The correlation between the expression of target genes and prognosis of GC was explored by using Kaplan Meier Plotter and GEPIA database. Results Venn diagram and differential gene screening analysis showed 21 upregulated genes in both datasets. GO analysis showed upregulated genes were mainly concentrated on responses to molecule of bacterial origin, CXCR chemokine receptor binding, positive regulation of neutrophil chemotaxis and other functions of related genes; the KEGG pathway mainly enriched in the pathways in cancer, TNF signaling pathway and chemokine signaling pathway. STRING and PPI database analysis showed an interaction among 9 of the 21 genes, PRDM1, IL10, NRP1, BIRC3, GNG13, CXCL1, CXCL2, CXCL3, CXCL8, which were the key genes. TCGA and Oncomine database displayed the overexpression of NRP1, CXCL1 and CXCL8 in GC, with statistical difference(all PConclusion The expression of NRP1, CXCL1 and CXCL8 were associated with H. pylori infection. These three genes were highly expressed in GC, especially the NRP1, which was associated with poor prognosis of GC.