首页|基于生物信息学探究NR1H4在慢性萎缩性胃炎及药物预测中的作用

基于生物信息学探究NR1H4在慢性萎缩性胃炎及药物预测中的作用

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目的 通过生物信息学方法获得慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的差异基因,预测治疗CAG的小分子药物.方法 通过基因表达综合(Gene Expression Omnibus,GEO)数据库获取 2 份 CAG 芯片(GSE27411、GSE116312)基因表达样本,利用 R 语言筛选出 CAG 差异表达基因,获得 CAG 免疫相关基因进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析.利用STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,筛选出核心基因,进一步研究核心基因的免疫浸润,预测其小分子化合物,通过MOE2022 进行分子对接,通过GEPIA2 网站进行生存分析.结果 基于GEO数据库筛选出差异基因 517 个.GO富集分析发现主要涉及粒细胞趋化性、白细胞趋化性、中性粒细胞趋化性等生物过程.KEGG富集分析显示主要富集于细胞因子-细胞因子受体相互作用通路、核因子κB信号通路、白细胞介素-17 信号通路.PPI网络筛选前 6 个核心基因即NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1,通过相关验证,NR1H4 作为核心基因.免疫细胞浸润分析结果显示中央记忆CD8 T细胞、效应记忆CD4 T细胞、γδT细胞、自然杀伤细胞、中性粒细胞等免疫细胞可能参与CAG的发生发展,而中性粒细胞与NR1H4 呈正相关.分子对接显示柯里拉京、豆甾醇、栀子苷、桔皮素、鹅去氧胆酸、表没食子儿茶素-3-没食子酸酯 6 种小分子药物与 NR1H4 有较好的结合力.结论 本研究初步探讨CAG的潜在机制,NR1H4 作为关键基因与中性粒细胞可能在CAG"炎-癌转化"进程中具有重要意义,可为CAG的"炎-癌转化"机制研究提供一定的参考依据.
Study on the role of NR1H4 in chronic atrophic gastritis and drug prediction based on bioinformatics
Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.

Chronic atrophic gastritisBioinformaticsNR1H4Differentially expressed genesImmune infiltration

彭晓婷、王文素、何典城、詹亚梅、游绍伟

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贵州中医药大学第二临床医学院,贵州贵阳 550002

贵州中医药大学第二附属医院干部保健科,贵州贵阳 550003

贵州中医药大学第二附属医院消化内科,贵州贵阳 550003

贵州省人民医院药剂科,贵州贵阳 550002

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慢性萎缩性胃炎 生物信息学 NR1H4 差异基因 免疫浸润

贵州省科技计划项目

黔科合基础-ZK[2022]一般502

2024

中国现代医生
中国医学科学院

中国现代医生

影响因子:1.571
ISSN:1673-9701
年,卷(期):2024.62(4)
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