骨关节炎的关键通路与免疫细胞浸润模式及中药预测分析

Key pathways and immune cell infiltration patterns in osteoarthritis and potential therapeutic prediction of Chinese herbs

目的 利用生物信息学的方法分析骨关节炎(osteoarthritis, OA)的关键通路与免疫细胞浸润模式及潜在治疗中药。方法 从基因表达综合数据库(GEO)中下载GSE55235基因表达芯片,运用GEO2R在线分析工具筛选差异表达基因(DEGs)。使用DAVID在线数据库对DEGs进行基因本体富集分析(Gene Ontology, GO)和京都基因与基因组百科全书信号通路分析(Kyoto Encyclopedia of Genes and Genomes, KEGG),通过STRING在线数据库构建蛋白相互作用网络(PPI)。使用Cytoscape软件中的cytoHubba插件筛选核心基因,Coremine Medical数据库预测治疗OA的潜在中药。通过CIBERSORT数据库对人类22种免疫细胞亚型的表达矩阵进行去卷积,分析OA组与对照组免疫细胞浸润情况。结果 共筛选出235个差异基因,其中101个为上调基因,134个为下调基因。GO富集分析主要涉及免疫反应、炎症反应、细胞粘附和凋亡过程等生物过程。KEGG主要富集在TNF信号通路、破骨细胞分化、MAPK信号通路、NF-kappa B信号通路、趋化因子信号通路、NOD样受体信号通路、Toll样受体信号通路等。通过PPI网络筛选出了IL6、IL1β、MMP9、PTGS2、VEGFA和CXCL8等10个核心基因,与Coremine Medical数据库相互映射筛选出郁金、姜黄和黄芩等治疗OA的潜在中药。免疫浸润分析结果显示,OA组织中B细胞和肥大细胞的浸润程度与对照组存在显著差异(P<0.05)。结论 本研究利用生物信息学的方法分析了OA的关键通路、免疫细胞浸润模式和潜在治疗中药,为OA发病机制和药物治疗提供了一定参考和借鉴。

Objective To analyze the key pathways and immune cell infiltration patterns in osteoarthritis(OA) and potential therapeutic prediction of Chinese herbs based on bioinformatics methods.Methods The GSE55235 gene expression chip was downloaded from the comprehensive gene expression database(GEO), and the differentially expressed genes(DEGs) were screened by the GEO2R online analysis tool. Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed using the DAVID database, and the protein-protein interaction(PPI) network was constructed through the STRING database. Core genes were screened by using the cytoHubba plug-in in Cytoscape software, and the core mine medical database predicted potential Chinese medicines for OA. The expression matrix of the 22 subtypes of human immune cells was deconvolved by the CIBERSORT database to analyze the infiltration of immune cells in the OA group and control groups.Results A total of 235 differentially expressed genes were selected, of which 101 were upregulated and 134 were downregulated. GO enrichment analysis mainly involved biological processes such as immune response, inflammatory response, cell adhesion, and apoptotic processes. KEGG was mainly enriched in the TNF signaling pathway, osteoclast differentiation, MAPK signaling pathway, NF-kappa B signaling pathway, chemokine signaling pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. The PPI network screened 10 core genes, including IL6, IL1β, MMP9, PTGS2, VEGFA and CXCL8, and selected the potential traditional Chinese medicines Yujin, Jianghuang and Huangqin for treating OA. The results of the immune infiltration analysis showed that the infiltration degree of B cells and mast cells in the OA tissues was significantly different from that of the control group(P<0.05).Conclusion In this study, the key pathways and immune cell infiltration patterns of OA and potential therapeutic prediction of Chinese herbs were analyzed by bioinformatics methods, which provide some reference for the pathogenesis and drug treatment of OA.