基于生物信息学分析儿童特发性血小板减少性紫癜的发病机制-东南大学学报医学版

基于生物信息学分析儿童特发性血小板减少性紫癜的发病机制

单位：1. 河南中医药大学儿科医学院, 河南郑州 450000;
2. 河南中医药大学第二附属医院儿科, 河南郑州 450002

分类号：R725.5

出版年·卷·期（页码）：2023·42·第二期（195-202）

摘要：

目的:基于生物信息学技术探讨儿童特发性血小板减少性紫癜(ITP)的发病机制。方法:通过检索Gene Expression Omnibus数据库获取儿童ITP相关芯片数据,通过GEO2R在线分析工具筛选出ITP患儿与正常儿童之间的差异表达基因(DEGs)。将得到的DEGs利用DAVID数据网站进行GO注释和KEGG通路富集分析,利用STRING数据库和Cytoscape软件构建了蛋白相互作用网络(PPT)并分析其核心靶点。最后对芯片数据集进行基因集富集分析(GSEA)和免疫细胞浸润分析(ICI)。结果:最终获取DEGs 276个,其中上调的有191个,下调的有85个。GO分析结果显示,DEGs主要富集于细胞基质黏附力、肥大细胞激活的负调控、细胞外基质组织、血红蛋白复合体等方面。KEGG分析显示,富集于受体酪氨酸激酶的抑制剂、ErbB信号通路、Rap1信号通路、轴突导向、PI3K-Akt信号通路及补体和凝血系统等。GSEA分析结果显示,在神经信号传递通路、黑色素瘤、细胞外基质受体相互作用、调节肌动蛋白细胞骨架、黏着斑等方面富集显著。ICI分析提示,ITP 组M2巨噬细胞和滤泡辅助性T细胞相对含量增加,激活的树突状细胞和静息的记忆CD4⁺T细胞相对含量减少。结论:儿童ITP的发病可能是由于ITGB3、ARRB1、COL3A1、COL11A1、CFTR等基因的异常表达,通过神经活性配体-受体相互作用、整合素受体结合、细胞黏附调节等生物过程,以及介导ErbB和PI3K-Akt信号通路从而造成免疫细胞的异常表达和血小板的减少。

Objective: To investigate the pathogenesis of idiopathic thrombocytopenic purpura(ITP) in children based on bioinformatics technology. Methods: In this study, we obtained microarray data related to childhood ITP by searching the Gene Expression Omnibus database, and screened the differentially expressed genes(DEGs) between children with ITP and normal children by using the GEO2R online analysis tool. The obtained DEGs were subjected to GO annotation and KEGG pathway enrichment analysis through the DAVID data website, and the protein interaction network(PPT) was constructed and analyzed for core targets using the STRING database and Cytoscape software. Finally, gene set enrichment analysis(GSEA) and immune cell infiltration analysis(ICI) were performed on the microarray data set. Results: 276 DEGs were obtained, of which 191 were up-regulated and 85 were down-regulated. GO analysis showed that DEGs were mainly enriched in cell matrix adhesion, negative regulation of mast cell activation, extracellular matrix organization, and hemoglobin complex. KEGG analysis showed enrichment in inhibitors of receptor tyrosine kinases, ErbB signaling pathway, Rap1 signaling pathway axon guidance, PI3K-Akt signaling pathway, and complement and coagulation systems. GSEA analysis showed significant enrichment in neural signaling pathways, melanoma, extracellular matrix receptor interactions, regulation of the actin cytoskeleton, and adhesive plaques. ICI analysis suggested an increase in the relative content of M2 macrophages and follicular helper T cells in the ITP group, activated dendritic cells and resting memory CD4⁺ T cells were reduced. Conclusion: The pathogenesis of ITP in children may be due to abnormal expression of genes such as ITGB3, ARRB1, COL3A1, COL11A1, and CFTR through biological processes such as neuroactive ligand-receptor interactions, integrin receptor binding, cell adhesion regulation, and mediation of ErbB and PI3K-Akt signaling pathways thereby causing immune cell abnormal expression and reduction of platelets.

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