Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Dermatology, Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Genet Test Mol Biomarkers. 2023 Dec;27(12):370-383. doi: 10.1089/gtmb.2023.0264.
The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. expression was associated with upregulation of hub genes including and in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, could regulate the production of downstream inflammatory factors. The IHC study revealed that was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.
本研究旨在表征与特应性皮炎（AD）中细胞焦亡相关的关键生物标志物。为了鉴定差异表达的细胞焦亡相关基因（DEPRGs），我们从基因表达综合数据库（GEO）中利用基因表达谱 GSE16161 和 GSE32924。进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路分析，以确定潜在的生物学功能和涉及的通路。此外，还进行了蛋白质-蛋白质相互作用网络分析，以鉴定枢纽基因。使用 CIBERSORT 进行免疫过滤分析，检测浸润免疫细胞的类型和比例。利用 miRNet 数据库构建 12 轴竞争内源性 RNA（ceRNA）网络。免疫组织化学（IHC）进一步验证了 AD 患者皮肤组织中关键基因的差异表达。本研究中人类受试者皮肤组织的采集经岳阳中西医结合医院伦理委员会审查和批准（KYSKSB2020-125）。研究共鉴定出 76 个 DEPRGs，这些基因富集在与炎症反应和免疫调节相关的基因中。AD 样本中激活的树突状细胞比例较高，静止的肥大细胞比例较低。在 ceRNA 网络中，与上调的枢纽基因包括和相关，并且与 AD 中的激活的树突状细胞相关。作为转录因子，IRF1 可以调节下游炎症因子的产生。免疫组化研究表明，IRF1 在 AD 患者的皮肤组织中过表达，与生物信息学研究结果一致。IRF1 和其相关基因被确定为 AD 中关键的细胞焦亡相关生物标志物，这是 AD 发病机制中的一个关键途径。
