基于综合生物信息学的急性心肌梗死相关枢纽基因及免疫浸润机制分析
Integrated Bioinformatics-Based Analysis of Hub Genes and the Mechanism of Immune Infiltration Associated With Acute Myocardial Infarction.
作者信息
Wu Yanze, Jiang Ting, Hua Jinghai, Xiong Zhiping, Chen Hui, Li Lei, Peng Jingtian, Xiong Wenjun
机构信息
Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Medical College, Nanchang University, Nanchang, China.
出版信息
Front Cardiovasc Med. 2022 Apr 6;9:831605. doi: 10.3389/fcvm.2022.831605. eCollection 2022.
BACKGROUND
Acute myocardial infarction (AMI) is a fatal disease that causes high morbidity and mortality. It has been reported that AMI is associated with immune cell infiltration. Now, we aimed to identify the potential diagnostic biomarkers of AMI and uncover the immune cell infiltration profile of AMI.
METHODS
From the Gene Expression Omnibus (GEO) data set, three data sets (GSE48060, GSE60993, and GSE66360) were downloaded. Differentially expressed genes (DEGs) from AMI and healthy control samples were screened. Furthermore, DEGs were performed gene ontology (GO) functional and kyoto encyclopedia of genes and genome (KEGG) pathway analyses. The Gene set enrichment analysis (GSEA) was used to analyze GO terms and KEGG pathways. Utilizing the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction (PPI) network was constructed, and the hub genes were identified. Then, the receiver operating characteristic (ROC) curves were constructed to analyze the diagnostic value of hub genes. And, the diagnostic value of hub genes was further validated in an independent data set GSE61144. Finally, CIBERSORT was used to represent the compositional patterns of the 22 types of immune cell fractions in AMI.
RESULTS
A total of 71 DEGs were identified. These DEGs were mainly enriched in immune response and immune-related pathways. Toll-like receptor 2 (TLR2), interleukin-1B (IL1B), leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2), Fc fragment of IgE receptor Ig (FCER1G), formyl peptide receptor 1 (FPR1), and matrix metalloproteinase 9 (MMP9) were identified as diagnostic markers with the value of < 0.05. Also, the immune cell infiltration analysis indicated that TLR2, IL1B, LILRB2, FCER1G, FPR1, and MMP9 were correlated with neutrophils, monocytes, resting natural killer (NK) cells, gamma delta T cells, and CD4 memory resting T cells. The fractions of monocytes and neutrophils were significantly higher in AMI tissues than in control tissues.
CONCLUSION
TLR2, IL1B, LILRB2, FCER1G, FPR1, and MMP9 are involved in the process of AMI, which can be used as molecular biomarkers for the screening and diagnosis of AMI. In addition, the immune system plays a vital role in the occurrence and progression of AMI.
背景
急性心肌梗死（AMI）是一种致命疾病，具有高发病率和死亡率。据报道，AMI与免疫细胞浸润有关。现在，我们旨在确定AMI的潜在诊断生物标志物，并揭示AMI的免疫细胞浸润特征。
方法
从基因表达综合数据库（GEO）下载了三个数据集（GSE48060、GSE60993和GSE66360）。筛选AMI和健康对照样本中的差异表达基因（DEG）。此外，对DEG进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路分析。使用基因集富集分析（GSEA）来分析GO术语和KEGG通路。利用搜索互作基因/蛋白的工具（STRING）数据库构建蛋白质-蛋白质相互作用（PPI）网络，并鉴定枢纽基因。然后，构建受试者工作特征（ROC）曲线以分析枢纽基因的诊断价值。并且，在独立数据集GSE61144中进一步验证枢纽基因的诊断价值。最后，使用CIBERSORT来呈现AMI中22种免疫细胞组分的组成模式。
结果
共鉴定出71个DEG。这些DEG主要富集于免疫反应和免疫相关通路。Toll样受体2（TLR2）、白细胞介素-1B（IL1B）、白细胞免疫球蛋白样受体亚家族B2（LILRB2）、IgE受体Ig的Fc片段（FCER1G）、甲酰肽受体1（FPR1）和基质金属蛋白酶9（MMP9）被鉴定为诊断标志物，其P值<0.05。此外，免疫细胞浸润分析表明，TLR2、IL1B、LILRB2、FCER1G、FPR1和MMP与中性粒细胞、单核细胞、静息自然杀伤（NK）细胞、γδT细胞和CD4记忆静息T细胞相关。AMI组织中单核细胞和中性粒细胞的比例显著高于对照组织。
结论
TLR2、IL1B、LILRB2、FCER1G、FPR1和MMP9参与AMI的发生过程，可作为AMI筛查和诊断的分子生物标志物。此外，免疫系统在AMI的发生和发展中起着至关重要的作用。
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