Predicting Diagnostic Gene Biomarkers Associated With Immune Checkpoints, N6-Methyladenosine, and Ferroptosis in Patients With Acute Myocardial Infarction.

Xiao Tong,Xuan Dang,Yan Kou,Junjie Kou,Xinyi Zhao

doi:10.3389/fcvm.2022.836067

Abstract

This study aimed to determine early diagnosis genes of acute myocardial infarction (AMI) and then validate their association with ferroptosis, immune checkpoints, and N6-methyladenosine (m6A), which may provide a potential method for the early diagnosis of AMI. Firstly, we downloaded microarray data from NCBI (GSE61144, GSE60993, and GSE42148) and identified differentially expressed genes (DEGs) in samples from healthy subjects and patients with AMI. Also, we performed systematic gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used STRING to predict protein interactions. Moreover, MCC and MCODE algorithms in the cytoHubba plug-in were used to screen nine key genes in the network. We then determined the diagnostic significance of the nine obtained DEGs by plotting receiver operating characteristic curves using a multiscale curvature classification algorithm. Meanwhile, we investigated the relationship between AMI and immune checkpoints, ferroptosis, and m6A. In addition, we further validated the key genes through the GSE66360 dataset and consequently obtained nine specific genes that can be used as early diagnosis biomarkers for AMI. Through screening, we identified 210 DEGs, including 53 downregulated and 157 upregulated genes. According to GO, KEGG, and key gene screening results, FPR1, CXCR1, ELANE, TLR2, S100A12, TLR4, CXCL8, FPR2 and CAMP could be used for early prediction of AMI. Finally, we found that AMI was associated with ferroptosis, immune checkpoints, and m6A and FPR1, CXCR1, ELANE, TLR2, S100A12, TLR4, CXCL8, FPR2 and CAMP are effective markers for the diagnosis of AMI, which can provide new prospects for future studies on the pathogenesis of AMI.

Highlights

Coronary heart disease affects 17.1 million people worldwide and results in a considerable number of fatalities, making it a global health concern [1]
Using the “clusterProfiler” package in Bioconductor and the gene function spectrum obtained through enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we found that differentially expressed genes (DEGs) were mainly concentrated in the following functional categories: Neutrophil extracellular trap formation, Lipid and atherosclerosis, IL−17 signaling pathway, Cytokine– cytokine receptor interaction, response to molecule of bacterial origin, neutrophil degranulation, neutrophil activation involved in immune response, defense response to bacterium (Figure 2)
We validated the association of acute myocardial infarction (AMI) with immune checkpoints, ferroptosis, and m6A

Summary

Introduction

Coronary heart disease affects 17.1 million people worldwide and results in a considerable number of fatalities, making it a global health concern [1]. Acute myocardial infarction (AMI) is one of the most serious ischemic heart diseases caused by the rupture of atherosclerotic plaque [2–4]. And correct diagnosis may be of great benefit in treatment [5–7]. Diagnostic Biomarkers of AMI several risk factors associated with the onset of AMI, including age, gender, hypertension, diabetes, smoking, alcohol consumption, and physical labor [8–11]. There is growing evidence that genetic factors contribute to the development of AMI [12]. Various therapeutic targets for AMI have been identified through the study of genetic factors such as mRNA [13–16]. It is necessary to explore new biomarkers with high sensitivity and specificity for the diagnosis of cardiovascular disease

Objectives

Methods

Results

Conclusion