Comprehensive analysis of autophagy-related genes and patterns of immune cell infiltration in valvular atrial fibrillation

Abstract

Background The development of atrial fibrillation (AF) following valvular heart disease (VHD) remains a common disease and is associated with substantial adverse complications. However, valid molecular diagnostic and therapeutic tools for post-VHD AF have not been fully established. This study was conducted to discover the molecular mechanisms and immune microenvironment underlying AF following VHD. Methods Gene expression profiles of the GSE41177 dataset were assessed to construct a protein–protein interaction network, and then, autophagy-related hub genes were identified. In addition, to determine the functions of immune cell infiltration in valvular AF, we used the CIBERSORT algorithm to estimate the composition of 22 immune cell types in valvular heart disease. Finally, correlation analysis was carried out to identify the relationship between differentially expressed autophagy-related genes (DEARGs) and significant immune cell subpopulations to reveal potential regulatory pathways. Results A total of 153 DEARGs were identified in AF-VHD patients compared with controlled donors. Moreover, we screened the top ten hub nodes with the highest degrees through a network analysis. The ten hub nodes were considered hub genes related to AF genesis and progression. Then, we revealed six significant immune cell subpopulations through the CIBERSORT algorithm. Finally, correlation analysis was performed, and six DEARGs (BECN1, GAPDH, ATG7, MAPK3, BCL2L1, and MYC) and three immune cell subpopulations (T cells CD4 memory resting, T cells follicular helper, and neutrophils) were identified as the most significant potential regulators. Conclusion The DEARGs and immune cells identified in our study may be critical in AF development following VHD and provide potential predictive markers and therapeutic targets for determining a treatment strategy for AF patients.

Identification and Validation of Autophagy-Related Genes as Potential Biomarkers and Therapeutic Targets in Atrial Fibrillation

“…Although Liu et al have previously conducted bioinformatics analysis of ARGs and AF, they only analyzed one dataset and did not verify the results. 17 In this study, we analyzed two datasets and verified the finally identified differential ARGs in patients with AF and non-AF individuals, which further improved the reliability of the results.…”

Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation

“…Liu et al also noticed that BECN1 , ATG7 , BCL2L1 and MYC , as novel molecular markers for the diagnosis of valvular atrial fibrillation, were positively correlated with the infiltration of neutrophils and negatively correlated with the infiltration of memory resting CD4 T cells and T follicular helper cells. Meanwhile, they found that the fractions of memory resting CD4 T cells and T follicular helper cells were decreased, and the fractions of resting dendritic cells, plasma cells, neutrophils, and monocytes were significantly increased in AF patients compared with SR subjects [ 26 ]. These results partially elucidated the pattern of immune cell infiltration in AF and identified several new molecular markers associated with the pathogenesis of AF.…”

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

“…Liu et al showed that mast cells and neutrophils were increased in AF atrial tissue in comparison to matched SR atrial tissue ( 47 ). In addition, Liu et al suggested that resting memory CD4 T cells and follicular helper T cells were decreased and that plasma cells, monocytes, resting dendritic cells, and neutrophils were increased in AF samples compared with SR samples ( 48 ). Nevertheless, different patterns of immune cell infiltration in AF were observed in the current study compared with previous studies.…”