Identification and Analysis of Hub Genes and Immune Cells Associated with the Formation of Acute Aortic Dissection.

Abstract

Acute type A aortic dissection (AAD) is a catastrophic disease with high mortality, but the pathogenesis has not been fully elucidated. This study is aimed at identifying hub genes and immune cells associated with the pathogenesis of AAD. The datasets were downloaded from Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA), gene set variation analysis (GSVA), and differential analysis were performed. The differentially expressed genes (DEGs) were intersected with specific genes collected from MSigDB. The gene function and pathway enrichment analysis were also performed on intersecting genes. The key modules were selected by weighted gene coexpression network analysis (WGCNA). Hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis and were verified in the metadataset. The immune cell infiltration was analyzed by CIBERSORT, and the relationship between hub genes and immune cells was performed by Pearson's correlation analysis. The single-cell RNA sequencing (scRNA-seq) dataset was used to verify the differences in DNA damage and repair signaling pathways and hub genes in different cell types. The results of GSEA and GSVA indicated that DNA damage and repair processes were activated in the occurrence of AAD. The gene function and pathway enrichment analysis on differentially expressed DNA damage- and repair-related genes showed that these genes were mainly involved in the regulation of the cell cycle process, cellular response to DNA damage stimulus, response to wounding, p53 signaling pathway, and cellular senescence. Three key modules were identified by WGCNA. Five genes were screened as hub genes, including CDK2, EIF4A1, GLRX, NNMT, and SLCO2A1. Naive B cells and Gamma delta T cells (γδ T cells) were decreased in AAD, but monocytes and M0 macrophages were increased. scRNA-seq analysis included that DNA damage and repair processes were activated in smooth muscle cells (SMCs), tissue stem cells, and monocytes in the aortic wall of patients with AAD. Our results suggested that DNA damage- and repair-related genes may be involved in the occurrence of AAD by regulating many biological processes. The hub genes and immune cells reported in this study also increase the understanding of AAD.