Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.
Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.
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使用生物信息学方法的增生性糖尿病性视网膜病的血管内皮细胞中枢纽基因与免疫细胞浸润之间的关系的鉴定。
DOI：
10.1155/2022/7231046
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Huang J;Zhou Q
糖尿病视网膜病变（diabetic retinopathy，DR）是一种严重的致盲眼病，尤其是在增殖期。然而，其对内皮细胞作用的发病机制，特别是其与免疫细胞浸润的关系仍不清楚。 从Gene Expression Omnibus（GEO）数据库下载数据集GSE 94019以获得DEG。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径富集分析等聚合分析，构建蛋白质相互作用（PPI）网络，分析DEG的潜在功能。采用加权基因共表达网络分析（WGCNA）和Cytoscape软件（包括分子复合物检测（MCODE）和cytoHubba插件）综合分析和确定枢纽基因。进行ImmuCellAI分析以进一步研究样品、枢纽基因和24种类型的免疫细胞浸润之间的关系。最后，基因集富集分析（GSEA）被用来确定富集的免疫细胞浸润和内皮细胞表型修饰的GO生物过程（BP）的基础上的枢纽基因的表达水平。 共鉴定出2393个DEG，其中800个基因表达下调，1593个基因表达上调。功能富集的结果显示，1398 BP术语在DEG中有显著富集。使用WGCNA和Cytoscape软件联合分析确定的3个枢纽基因EEF1A1、RPL 11和RPS 27 A与CD4幼稚T细胞数量呈正相关，与B细胞数量呈负相关。与非糖尿病组相比，糖尿病组CD4幼稚T细胞、辅助性T细胞2（Th2）和效应记忆性T细胞（Tem）数量显著增加，而CD8幼稚T细胞和B细胞数量显著减少。 我们发现了与PDR发病机制相关的内皮细胞DEGs和Hub基因：EEF1A1、RPL 11和RPS 27 A，它们彼此高度相关，并参与炎症相关的免疫细胞浸润和内皮细胞发育、趋化性和增殖的特异性生物学过程，从而为PDR的诊断和潜在的“一石二鸟”靶向治疗提供了新的视角。
Diabetic retinopathy (DR) is a serious ophthalmopathy that causes blindness, especially in the proliferative stage. However, the pathogenesis of its effect on endothelial cells, especially its relationship with immune cell infiltration, remains unclear. The dataset GSE94019 was downloaded from the Gene Expression Omnibus (GEO) database to obtain DEGs. Through aggregate analyses such as Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis, a protein-protein interaction (PPI) network was constructed to analyze the potential function of DEGs. Weighted gene coexpression network analysis (WGCNA) and Cytoscape software including molecular complex detection (MCODE) and cytoHubba plug-ins were used to comprehensively analyze and determine the hub genes. ImmuCellAI analysis was performed to further study the relationship between samples, hub genes, and 24 types of immune cell infiltration. Finally, gene-set enrichment analysis (GSEA) was employed to identify the enrichment of immune cell infiltration and endothelial cell phenotype modifications in GO biological processes (BP) based on the expression level of hub genes. 2393 DEGs were identified, of which 800 genes were downregulated, and 1593 genes were upregulated. The results of functional enrichment revealed that 1398 BP terms were significantly enriched in DEGs. Three hub genes, EEF1A1, RPL11, and RPS27A, which were identified by conjoint analysis using WGCNA and Cytoscape software, were positively correlated with the number of CD4 naive T cells and negatively correlated with the numbers of B cells. The number of CD4 naive T cells, T helper 2 (Th2) cells, and effector memory T (Tem) cells were significantly higher while CD8 naive T cells and B cells significantly were lower in the diabetic group than in the nondiabetic group. We unearthed the DEGs and Hub genes of endothelial cells related to the pathogenesis of PDR: EEF1A1, RPL11, and RPS27A, which are highly related to each other and participate in the specific biological process of inflammation-related immune cell infiltration and endothelial cell development, chemotaxis, and proliferation, thus providing new perspectives into the diagnosis of and potential “killing two birds with one stone” targeted therapy for PDR.
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