Co-expression and interaction network analysis identifies neutrophil-related genes as the core mediator of atrial fibrillation.

ABSTRACT

Atrial fibrillation (AF) is the most common cardiac arrhythmia and can cause serious complications. Several studies have shown that neutrophils may influence AF progression. However, the key genes related to neutrophils in AF have not been fully elucidated. Here, we downloaded microarray expression data of AF, and screened differentially expressed genes. Key immune cells in AF were identified by immune cell infiltration analysis. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis were used to construct gene co-expression modules and identify hub genes. The association between key genes and neutrophils was then verified. Our results showed that 303 differentially expressed genes (DEGs) were screened in AF and sinus rhythm (SR), of which 194 were up-regulated and 109 were down-regulated. DEGs were mainly enriched in functions and pathways of neutrophil activation and biological functions of neutrophil activation-mediated immune response. Immune infiltration analysis revealed elevated levels of neutrophil infiltration in AF. WGCNA analysis revealed that the modules in dark red were associated with neutrophils. PPI analysis of these modules yielded 10 hub genes. S100A12, FCGR3B and S100A8 are 3 potential key genes related to neutrophils in AF, which are significantly positively correlated with neutrophils. These genes deserve further investigation and may be potential therapeutic targets for AF.