Identification and analysis of cuproptosis associated molecular clusters and immunological profiles in atopic dermatitis.

Background: Atopic dermatitis (AD) is a chronic skin condition marked by persistent itching and dryness. The role of cuproptosis, a novel form of programmed cell death, in AD is not yet understood.

Methods: The GSE107361 dataset was obtained from the Gene Expression Omnibus (GEO) database. Cuproptosis-related genes (CRGs) in AD were identified and analyzed, and immune landscape analysis was performed using ssGSEA. AD was clustered based on CRGs using ConsensusClusterPlus. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were conducted. Hub genes between AD clusters were identified, and both protein-protein interaction (PPI) and drug-gene interaction networks were developed.

Results: Three CRGs (DLD, MTF1, and GLS) were significantly upregulated in the AD group compared to healthy controls. Notably, four core CRGs (LIAS, LIPT1, PDHA1, CDKN2A) distinguished early-onset from adult-onset AD, indicating more active cuproptosis in early-onset AD. CRGs were linked to immune cell infiltration in AD, highlighting differences in immune microenvironments between early- and adult-onset AD. Early-onset AD showed high innate immunity, while adult-onset AD had a mix of innate and type 1 adaptive immunity. CRG expression identified two molecular subtypes with distinct immune infiltration: Cluster 2 (high cuproptosis) had predominant innate immunity, while Cluster 1 (low cuproptosis) had adaptive immunity. Additionally, 102 hub DEGs were identified through WGCNA co-expression network analysis, and 10 hub node genes were identified and potential drugs were explored for the management of AD.

Conclusions: The study provides insights into the roles of cuproptosis-related processes in the pathogenesis and potential treatment of AD. Finding of key hub genes between the 2 distinct immune infiltration subtypes might inform potential therapeutic strategies for AD.