Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis.

Abstract

Atrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism and analyze immune infiltration in DCM complicated with AF through comprehensive bioinformatics analysis. The gene expression datasets of DCM (GSE141910) and AF (GSE41177 and GSE79768) were obtained from the Gene Expression Omnibus database. Gene enrichment analyses were performed after screening the common differentially expressed genes (DEGs) of DCM and AF. Protein-protein interaction network was constructed in the STRING database and visualized in Cytoscape software, which helped to further screen the central functional modules of DEGs and hub genes. In addition, ImmuCellAI algorithm was performed to estimate immune infiltration patterns, and Spearman correlation was conducted to investigate the correlation between the abundance of multiple immune cells and the expression levels of hub immune-related genes after obtaining hub immune-related genes from the ImmPort database. The hub immune-related genes expression and immune infiltration patterns were additionally verified in the validation datasets (GSE57338, GSE115574, and GSE31821). The diagnostic effectiveness of hub immune-related genes was evaluated through Receiver Operator Characteristic Curve analysis. A total of 184 common DEGs in DCM and AF were identified for subsequent analyses. The functions of hub genes were significantly associated with immune responses. We identified 7 hub immune-related genes (HLA-DRA, LCK, ITK, CD48, CD247, CD3D, and IL2RG) and a spectrum of immune cell subsets including Monocyte, Neutrophil, and follicular helper T (Tfh) cells were found to be concurrently dysregulated in both DCM and AF. 7 hub immune-related genes were predominantly favorably correlated with Tfh cells and were primarily negatively correlated with Neutrophil infiltrations in DCM and AF. CD48+CD3D were verified to diagnose DCM and AF with excellent sensitivity and specificity, showing favorable diagnostic value. Our study reveals that immune cells (Tfh cells) disorders caused by hub immune-related genes (CD48 and CD3D) may be the common pathogenesis of DCM combined with AF, which lays a foundation for further immune mechanism research.