Wang Liangzhe, Wang Bo, Peng Min, Yang Xiaoyan, Huang Sijia, Wang Ruixin, Du Lin, Yao Ruiqian, Wang Wei, Dong Baiping, Zhu Yuanjie
Department of Dermatology, Naval Medical Center, Naval Medical University, Shanghai, China.
Department of Ultrasound Diagnosis, Naval Medical Center, Naval Medical University, Shanghai, China.
Front Immunol. 2025 Jun 27;16:1545457. doi: 10.3389/fimmu.2025.1545457. eCollection 2025.
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.
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.
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.
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.
特应性皮炎（AD）是一种以持续性瘙痒和干燥为特征的慢性皮肤病。铜死亡作为一种新型程序性细胞死亡形式，在AD中的作用尚不清楚。
从基因表达综合数据库（GEO）中获取GSE107361数据集。鉴定并分析AD中与铜死亡相关的基因（CRGs），并使用单样本基因集富集分析（ssGSEA）进行免疫景观分析。基于CRGs使用ConsensusClusterPlus对AD进行聚类。进行加权基因共表达网络分析（WGCNA）和差异基因表达分析。确定AD聚类之间的枢纽基因，并构建蛋白质-蛋白质相互作用（PPI）和药物-基因相互作用网络。
与健康对照相比，AD组中三个CRGs（DLD、MTF1和GLS）显著上调。值得注意的是，四个核心CRGs（LIAS、LIPT1、PDHA1、CDKN2A）区分了早发型和成人型AD，表明早发型AD中铜死亡更活跃。CRGs与AD中的免疫细胞浸润相关，突出了早发型和成人型AD免疫微环境的差异。早发型AD表现出高固有免疫，而成人型AD具有固有免疫和1型适应性免疫的混合特征。CRG表达确定了两种具有不同免疫浸润的分子亚型：聚类2（高铜死亡）具有主要的固有免疫，而聚类1（低铜死亡）具有适应性免疫。此外，通过WGCNA共表达网络分析确定了102个枢纽差异表达基因（DEGs），并确定了10个枢纽节点基因，并探索了用于AD治疗的潜在药物。
该研究为铜死亡相关过程在AD发病机制和潜在治疗中的作用提供了见解。在两种不同免疫浸润亚型之间发现关键枢纽基因可能为AD的潜在治疗策略提供依据。
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