吉林大学学报（医学版）2024，Vol.50Issue(3)：749-758,10.DOI:10.13481/j.1671-587X.20240319
基于经皮冠状动脉介入治疗术后支架内再狭窄的免疫相关基因及免疫细胞浸润的生物信息学分析
Bioinformatics analysis based on immune-related genes and immune cell infiltration of in-stent restenosis after percutaneous coronary intervention
摘要
Abstract
Objective:To screen the differentially expressed immune-related genes(DEIRGs)in in-stent restenosis(ISR),and to analyze the immune cell infiltration in ISR,and to clarify the mechanism of occurrence and development of ISR.Methods:The mRNA gene expression data of GSE46560 dataset samples were downloaded from the Gene Expression Omnibus(GEO),and divided into ISR group and non-ISR group.The"Limma"package in R software was used to identify the differentially expressed genes(DEGs)which were then intersected with immune-related genes(IRGs)to identify the DEIRGs in ISR;R software was used for Gene Ontology(GO)functional enrichment andalysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis on DEIRGs;the STRING database was used to construct the protein-protein interaction(PPI)network,which was visualized and analyzed for Hub genes by Cytoscape software;the receiver operating characteristic(ROC)curve of the Hub genes were plotted,and the area under the curve(AUC)was calculated and the diagnostic value was evaluated;CIBERSORT software was used to analyze the immune cell infiltration in ISR;Pearson correlation analysis was used to analyze the relationships between the immune cells and the relationships between the immune cells and key genes.Results:A total of 331 DEGs were identified(P<0.05,|log2FC|>1),including 176 upregulated genes and 155 downregulated genes,and 38 DEIRGs were obstained.The GO functional enrichment analysis results showed that the DEIRGs were mainly enriched in biological processes(BP)such as defense response,immune response,and immune system;in cellular components(CC),the DEIRGs were located primarily in the extracellular region and cytoplasmic membrane;and in molecular functions(MF),the DEIRGs were mainly involved in regulating signaling receptor binding and cytokine receptor activity.The KEGG signaling pathway enrichment analysis results indicated that the DEIRGs in ISR were primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and transforming growth factor-β(TGF-β)signaling pathways.In the PPI network,CD19 had the highest node among the top 10 Hub genes.Compared with non-ISR group,the expression level of the CD19 gene in the samples in ISR group was increased(P<0.05).The AUC value in the ROC curve of CD19 gene expression was 0.92(P<0.05).The immune cell infiltration analysis results showed that compared with non-ISR group,the infiltration level of T lymphocyte follicular helper(Tfh)cells in the patients in ISR group were increased(P<0.05),the infiltration levels of immature B lymphocytes,CD8+T lymphocytes,naive CD4+T lymphocytes,and M0 macrophages were increased,but the differences were not statistically significant(P>0.05),while the infiltration levels of memory B lymphocytes,activated memory CD4+T lymphocytes,regulatory T cells,resting natural killer(NK)cells,activated NK cells,monocytes,resting mast cells,and neutrophils were decreased,but the differences were not statistically significant(P>0.05).There were positive correlations between Tfh cells and M0 macrophages and resting mast cells(r=0.88,P<0.05;r=0.68,P<0.05),and there were negative correlations between Tfh cells and monocytes and neutrophils(r=-0.49,P<0.05;r=-0.42,P<0.05).Conclusion:CD19 may influence the occurrence and development of ISR by regulating the activation of the PI3K-AKT signaling pathway to affect the Tfh and B lymphocytes.CD19 can serve as a biomarker for the diagnosis of ISR.关键词
支架内再狭窄/CD19/差异表达免疫相关基因/免疫浸润/生物标志物Key words
In-stent restenosis/CD19/Differentially expressed immune-related gene/Immune infiltration/Biomarker分类
医药卫生引用本文复制引用
冯玉飞,金珊,王玉冰,鲁印飞,庞丽娟,刘克坚..基于经皮冠状动脉介入治疗术后支架内再狭窄的免疫相关基因及免疫细胞浸润的生物信息学分析[J].吉林大学学报（医学版）,2024,50(3):749-758,10.基金项目
国家自然科学基金项目(82060054) （82060054）
新疆生产建设兵团科技局财政科技计划项目(2020BC003) （2020BC003）
广东省湛江市科技局科技发展基础研究专题专项(2022A01028) （2022A01028）
广东省湛江市科技局疾病防治重点项目(2022A01103) （2022A01103）
2022年度湛江中心人民医院院级高层次人才科研启动经费项目(2022A15,2022A16) （2022A15,2022A16）
石河子大学科研项目(ZZZC202022A) （ZZZC202022A）
新疆维吾尔自治区研究生教育创新计划项目(XJ2022G110) （XJ2022G110）
石河子大学第一附属医院博士基金项目(BS202205) （BS202205）
