Bioinformatics analysis of FCER1A as a key immune marker in dilated cardiomyopathy and systemic lupus erythematosus.

Abstract

Background: Systemic lupus erythematosus (SLE) and dilated cardiomyopathy (DCM) are closely linked biologically, especially regarding immune responses. However, key biomarkers mediating the onset and development of both diseases are still lacking. This study uses bioinformatic methods to analyse the immune microenvironment of the ventricles of DCM patients and to search for biomarkers related to DCM and SLE.

Methods: Single-cell and bulk transcriptomic data for DCM were obtained from the GEO database, while GWAS data for SLE were obtained from the FinnGen database. The SMR method was used to identify genetic variants in the ventricles associated with SLE. Differential analysis was used to detect genes specific to monocyte-macrophages. Subsequently, a combination of machine learning algorithms was employed to select hub genes. Finally, small molecule drugs targeting the hub genes were retrieved from the DGIdb database.

Results: Mononuclear macrophages were found to be significantly infiltrated in dilated cardiomyopathy (DCM) samples. Seven key genes (HLA-DQB1, CD52, FCER1A, etc.) were identified by cross-tabulation analysis, of which FCER1A was the best-performing (AUC 0.8-0.9) among ten machine learning models. Validation of multiple datasets showed that FCER1A was highly expressed in the DCM group, was mainly involved in the immune cell activation pathway, and strongly interacted with other cells in the myocardial microenvironment through the MK/PROS pathway. The gene was highly expressed in the middle and late stages of monocyte-macrophage differentiation and was associated with drugs such as benzathine penicillin polylysine and omalizumab.

Conclusion: FCER1A was found to be a key differentially expressed gene in mononuclear macrophages in DCM myocardial tissue, and its significantly high expression was closely associated with immune cell activation in the myocardial microenvironment, which lays a theoretical foundation for immunotherapy of DCM and requires further clinical validation.