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基于生物信息学分析变应性鼻炎的差异表达基因及发病机制探讨

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目的 应用生物信息学对变应性鼻炎患者与健康对照者的鼻黏膜细胞间差异表达基因进行分析,探索变应性鼻炎的发病机制及关键基因.方法 从GEO数据库中下载5名健康对照者鼻上皮细胞样品和7例变应性鼻炎患者鼻上皮细胞样品的芯片数据(GSE43523).应用R语言中"limma"包筛选差异表达基因;并运用STRING数据库来构建所筛选差异基因的蛋白质-蛋白质相互作用网络,利用Cytoscape中的"Cytohubba"筛选关键基因;并采用DAVID数据库对选定的差异性基因进行基因本体(GO)功能分析和京都基因和基因组数据库(KEGG)途径探讨;通过ImmuCellAI数据库分析GSE43523芯片数据的24类免疫细胞的含量及比例.选取2023年9月至12月青岛市中医医院耳鼻咽喉头颈外科在手术中收集的15例变应性鼻炎患者和15名健康对照者的下鼻甲黏膜组织用于进一步的关键基因表达水平的检测分析.结果 共筛选出274个差异表达基因,包含上调差异表达基因144个,下调差异表达基因130个.基于蛋白质-蛋白质相互作用网络中获取5个关键基因,即CD80、CD69、EPAS1、MYOM2和ATP12A.GO功能富集显示,在生物过程中,差异表达基因主要富集在生物合成过程、NF-κB信号通路等;在细胞组成中,差异表达基因主要涉及细胞外间隙、质膜的组成部分等;在分子功能中,差异表达基因参与NAD活性、ATP酶结合活性等.KEGG信号通路富集分析显示,差异表达基因主要集中在铁死亡信号通路、凋亡信号通路等.免疫浸润分析结果显示,变应性鼻炎患者与健康对照者在活化的CD4天然细胞、CD8天然细胞、单核细胞和嗜中性粒细胞中存在显著性差异.变应性鼻炎患者下鼻黏膜组织中CD80和EPAS1的mRNA表达水平低于健康对照者,而CD69、MYOM2和ATP12A的mRNA表达水平高于健康对照者(P<0.01).结论 本研究发现了274个与变应性鼻炎密切相关的差异表达基因,得到了5个重要基因,为变应性鼻炎的早期诊断、干预治疗以及新药研发提供了新的研究方向.
Analysis of differentially expressed genes and pathogenesis of allergic rhinitis based on bioinformatics
Objective To analyze the differentially expressed genes between the nasal mucosa cells of patients with allergic rhinitis and healthy controls by bioinformatics,and to explore the pathogenesis and key genes of allergic rhinitis.Methods Microarray data(GSE43523)of nasal epithelial cell samples from five healthy controls and seven patients with allergic rhinitis were downloaded from the GEO database.The"limma"package in R language was used to screen differentially expressed genes.In addition,STRING database was used to construct proteinprotein interaction network of the selected differential genes,and"Cytohubba"in Cytoscape was used to screen key genes.The selected differential genes were analyzed by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)using the DAVID database.The content and proportion of 24 types of immune cells in GSE43523 chip data were analyzed by ImmuCellAI database.The inferior turbinate mucosa tissues of 15 patients with allergic rhinitis and 15 healthy controls were collected from the Department of Otolaryngology and Head and Neck Surgery of Qingdao Hospital of Traditional Chinese Medicine,Shandong Province from September to December 2023 for further detection and analysis of key gene expression levels.Results A total of 274 differentially expressed genes were screened,including 144 up-regulated and 130 down-regulated genes.Five key genes,namely CD80,CD69,EPAS1,MYOM2,and ATP12A,were obtained based on proteinprotein interaction network.GO functional enrichment showed that in biological processes,differentially expressed genes were mainly concentrated in biosynthesis and NF-κB signaling pathway.In cellular component,differentially expressed genes were mainly involved in extracellular space and components of plasma membrane.In molecular function,differentially expressed genes participate in NAD activity and ATPase binding activity.KEGG signaling pathway enrichment analysis showed that differentially expressed genes were mainly concentrated in iron death signaling pathway and apoptosis signaling pathway.Immunoinfiltration analysis showed significant differences in activated CD4 natural cells,CD8 natural cells,monocytes,and neutrophils between patients with allergic rhinitis and healthy controls.The mRNA expression levels of CD80 and EPAS1 in the lower nasal mucosa of patients with allergic rhinitis were lower than those of healthy controls,while the mRNA expression levels of CD69,MYOM2,and ATP12A were higher than those of healthy controls(P<0.01).Conclusion In this study,274 differentially expressed genes closely related to allergic rhinitis were found,and five important genes were obtained,which provided a new research direction for early diagnosis,intervention,and new drug development of allergic rhinitis.

Allergic rhinitisBioinformatical analysisDifferential expression analysisHub genesImmunoinfiltration analysis

苏轶楣、滕腾、王倩倩、徐英、葛洪洲

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青岛大学附属青岛市海慈医院青岛市中医医院皮肤科,山东青岛 266033

青岛大学附属青岛市海慈医院青岛市中医医院耳鼻咽喉科,山东青岛 266033

变应性鼻炎 生物信息学分析 差异表达分析 关键基因 免疫浸润

2024

中国医药导报
中国医学科学院

中国医药导报

CSTPCD
影响因子:1.759
ISSN:1673-7210
年,卷(期):2024.21(24)