Identification of Potential Key Biomarkers of Atrial Fibrillation and Their Correlation with Immune Infiltration in Atrial Tissue.

ABSTRACT

Objective: To identify potential key biomarkers and characterize immune infiltration in atrial tissue of patients with atrial fibrillation (AF) through bioinformatics analysis. Methods: Differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional and pathway enrichment analyses were undertaken using GO and KEGG. The LASSO logistic regression and BORUTA algorithm were employed to screen for potential novel key markers of AF from all DEGs. Gene set variation analysis was also performed. Single-sample gene set enrichment analysis was employed to quantify the infiltration levels for each immune cell type, and the correlation between hub genes and infiltrating immune cells was analyzed. Results: A total of 52 DEGs were identified, including of 26 downregulated DEGs and 26 upregulated DEGs. DEGs were primarily enriched in the Major Histocompatibility Complex class II protein complex, glucose homeostasis, protein tetramerization, regulation of synapse organization, cytokine activity, heart morphogenesis, and blood circulation. Three downregulated genes and three upregulated genes were screened by LASSO logistic regression and the BORUTA algorithm. Finally, immune infiltration analysis indicated that the atrial tissue of AF patients contained significant infiltration of APC_co_inhibition, Mast_cell, neutrophils, pDCs, T_cell_costimulation, and Th1_cells compared with paired sinus rhythm (SR) atrial tissue, and the three downregulated genes were negatively correlated with the six kinds of immune cells mentioned above. Conclusion: The hub genes identified in this study and the differences in immune infiltration of atrial tissue observed between AF and SR tissue might help to characterize the occurrence and progression of AF.