Identification and Verification of Biomarkers and Immune Infiltration in Obesity-Related Atrial Fibrillation

SIMPLE SUMMARY: Obesity is an independent risk factor for atrial fibrillation, which, in the ensuing decades, will probably increase the global burden. Previous studies have indicated that inflammation is a central mediator between obesity and atrial fibrillation. However, the mechanisms underlying this crosstalk are still being uncovered, and there are insufficient specific biomarkers. We co-analyzed the atrial fibrillation and obesity microarrays to investigate the possible molecular mechanism of obesity-related atrial fibrillation. We found that MNDA, CYBB, CD86, FCGR2C, NCF2, LCP2, TLR8, HLA-DRA, LCP1, and PTPN22 were only elevated in blood samples of obese atrial-fibrillation patients. Atrial-fibrillation patients’ left atrial appendage had increased infiltration of naïve B cells and decreased infiltration of memory B cells. Ten validated hub genes were related positively to naïve B cells and negatively to memory B cells. Ten validated genes identified by bioinformatics analysis, specifically correlated with obesity-related atrial fibrillation, may serve as biomarkers for obesity-related atrial fibrillation. These findings may also aid in comprehending pathophysiological mechanisms and identifying possible treatment targets for obesity-related atrial fibrillation. ABSTRACT: Obesity is an independent risk factor for atrial fibrillation (AF). However, the mechanisms underlying this crosstalk are still being uncovered. Co-differentially expressed genes (co-DEGs) of AF and obesity microarrays were identified by bioinformatics analysis. Subsequently, functional enrichment, cell-type enrichment, and protein–protein interaction network analyses of co-DEGs were carried out. Then, we validated the hub genes by qRT-PCR of patients’ blood samples. Finally, CIBERSORT was utilized to evaluate the AF microarray to determine immune infiltration and the correlation between validated hub genes and immune cells. A total of 23 co-up-regulated DEGs in AF and obesity microarrays were identified, and these genes were enriched in inflammation- and immune-related function. The enriched cells were whole blood, CD33+ myeloid, and CD14+ monocytes. The hub genes were identified as MNDA, CYBB, CD86, FCGR2C, NCF2, LCP2, TLR8, HLA-DRA, LCP1, and PTPN22. All hub genes were only elevated in blood samples of obese-AF patients. The CIBERSORT analysis revealed that the AF patients’ left atrial appendage had increased infiltration of naïve B cells and decreased infiltration of memory B cells. The hub genes were related positively to naïve B cells and negatively to memory B cells. Ten hub genes may serve as biomarkers for obesity-related AF. These findings may also aid in comprehending pathophysiological mechanisms for obesity-related AF.