Identification of Immune Activation-Related Biomarkers in Acute Myocardial Infarction (AMI) by Bioinformatic Analysis and Clinical Validation
Abstract Background: Although reperfusion therapy is widely performed in patients with acute myocardial infarction (AMI), the residual risk of poor outcomes remains substantial. The immune system plays an important role in AMI, and therapies targeting immune cells have proved effective in improving prognosis after AMI. However, the activation and regulation of immune signaling pathways during AMI have not been systematically studied.Objective: This study aimed to reveal the activation status of immune-related signals and the immune status after AMI.Methods and results: Three publicly available datasets (GSE48060, GSE66360, and GSE97320) from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) using peripheral blood tissue samples from 22 AMI patients and 22 individuals without AMI. Subsequent weighted gene correlation network analysis (WGCNA) was performed for CD4+ T cells, macrophages, and regulatory T cells, and the 387 genes with the most significant correlations with the three immune cells were identified. Then, we intersected the 192 DEGs with 387 genes from WGCNA to reveal , a total of 151 overlapping genes. Protein-protein interaction (PPI) network analysis was performed to identify the hub genes. Furthermore, we recruited 44 patients and collected blood samples to validate the stability and reliability of the predicted hub tragets TLR2, TLR4, TLR8, MMP-9 and TYROBP using qRT-PCR assay.Conclusions: The immune-related genes TLR2, TLR4, TLR8, MMP9 and TYROBP may be potential biomarkers to identify immune signal activation after AMI, therefore providing information for the evaluation of both immune status and early intervention.