摘要
Abstract
Objective To decipher the immune characteristics of atherosclerotic ischemic stroke using multi-omics data.
Methods Atherosclerotic ischemic stroke-related genes were identified by integrating Mendelian randomization with transcriptomic data.Pathway functions were elucidated through gene set enrichment analysis and gene set variation analysis.The protein-protein interaction networks were constructed using the search tool for the retrieval of interacting genes/proteins(STRING)database,and hub genes were subsequently screened with Cytoscape software.Cell differentiation trajectories and communication networks were analyzed by combining single-cell sequencing data(using the SingleR and CellChat packages).Based on transcriptome data,the cell-type identification by estimating relative subsets of ribonucleic acid transcripts(CIBERSORT)algorithm was used to infer immune cell composition and quantify the relative abundance of different immune cell subsets.
Results A total of 133 atherosclerotic ischemic stroke-related genes were identified,with functional enrichment analysis indicating their involvement in vascular smooth muscle development(gene ontology:0097084).Cell communication analysis revealed that these genes regulate interactions among immune cells(such as microglia and monocytes)through eight ligand-receptor pairs of the secreted phosphoprotein 1 and galectin pathway.In the protein-protein interaction network,hub genes including senataxin(SETX),valosin containing protein(VCP),Fc fragment of IgG receptor Ⅱb(FCGR2B),cluster of differentiation 44(CD44)(OR＞1,positive causal relationship),C-X-C motif chemokine receptor 2(CXCR2),and sequestosome 1(SQSTM1)(OR＜1,negative causal relationship)were found to regulate immune cell differentiation and influence biological processes such as T help cells 2 cell regulation and suppression of inflammatory antigen response.CIBERSORT evaluation showed that CD8+T cells,activated natural killer(NK)cells,macrophages M0,resting mast cells,and neutrophils were associated with atherosclerotic ischemic stroke.Specifically,SETX expression was positively correlated with neutrophil infiltration(ρ=0.29),CD44 expression was positively correlated with infiltration of activated NK cells(ρ=0.29)and negatively correlated with neutrophil infiltration(ρ=-0.41).
Conclusions Hub genes such as SETX,VCP,FCGR2B,CD44,CXCR2,and SQSTM1 contribute to the pathological process of atherosclerotic ischemic stroke by regulating the differentiation of central and peripheral immune cells and vascular smooth muscle function,making them potential biomarkers.关键词
动脉粥样硬化型缺血性卒中/免疫微环境/单细胞测序/细胞分化/细胞通信Key words
Atherosclerotic ischemic stroke/Immune microenvironment/Single-cell sequencing/Cell differentiation/Cell communication分类
临床医学
