Integrated bioinformatic analysis of immune infiltration and disulfidptosis related gene subgroups in type A aortic...

Type A aortic dissection (TAAD) is a lethal cardiovascular disease characterized by the separation of the layers within the aortic wall. The underlying pathological mechanisms of TAAD requires further elucidation to develop effective prevention and pharmacological treatment strategies. Inflammation plays a crucial role in TAAD pathogenesis. Disulfidptosis, an emerging type of cell death, may shed light on disease mechanisms. This study investigates the role of disulfidptosis-related genes in immune infiltration in TAAD. TAAD gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. Immune cell infiltration analysis assessed immune cell dysregulation in TAAD. Differentially expressed genes (DEGs) between TAAD samples and controls were identified and intersected with known disulfidptosis-related gene sets to obtain relevant DEGs. Hub genes were identified using machine learning algorithms. A diagnostic model was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) regression on 25 TAAD samples. Consensus clustering classified TAAD samples based on disulfidptosis-related gene expression. Functional enrichment analyses, including Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, elucidated associated biological processes and pathways. A total of 13,316 DEGs were identified, among which 11 disulfidptosis-related genes were screened: INF2, CD2AP, PDLIM1, ACTN4, MYH10, MYH9, FLNA, FLNB, TLN1, MYL6, ACTB, CAPZB, DSTN, and IQGAP1. Most of these genes exhibited lower expression levels in TAAD samples, except CAPZB, and were correlated with immune cell infiltration. Cluster-specific DEGs were found in one cluster, involving several immune response processes. Co-clustering analysis based on disulfidptosis-related genes classified TAAD samples into two clusters, with higher gene expression levels observed in cluster C2 compared to cluster C1. Three key hub genes were identified, and potential therapeutic mechanisms for TAAD were explored. Immuno-infiltration results revealed significant differences in immune profiles, with higher immunological scores and more extensive immune infiltration in TAAD. Disulfidptosis occurs in TAAD and is associated with immune cell infiltration and metabolic activity, influencing immune cell function and responses. These findings suggest that disulfidptosis may promote TAAD progression through the induction of immune responses and metabolic activities. This research provides new insights into the pathogenesis and identifies potential therapeutic targets for TAAD.