Qiao Weizhou, Zhu Cuiping, Huang Dan, Liu Yue, Wang Zengkai, Zhu Tianjie, Song Qingyu, Yang Xu, Wang Yueying, Wang Yushuang
Department of Clinical Laboratory, Central Hospital of Dalian University of Technology, Dalian, 116033, People's Republic of China.
Blood Purification Center, Central Hospital of Dalian University of Technology, Dalian, 116033, People's Republic of China.
Clin Cosmet Investig Dermatol. 2025 Jan 9;18:61-76. doi: 10.2147/CCID.S492340. eCollection 2025.
Juvenile dermatomyositis (JDM) is a complex autoimmune disease, and its pathogenesis remains poorly understood. Building upon previous research on the immunological and inflammatory aspects of JDM, this study aims to investigate the role of pyroptosis in the pathogenesis of JDM using a comprehensive bioinformatics approach.
Two microarray datasets (GSE3307 and GSE11971) were obtained from the Gene Expression Omnibus database, and a list of 62 pyroptosis-related genes was compiled. Differential gene expression analysis and machine learning analysis were performed to identity the hub pyroptosis-related differentially expressed genes (PR-DEGs). Functional enrichment analysis, immune cell infiltration analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) were performed to elucidate the potential roles of PR-DEGs in JDM pathogenesis.
A total of 2526 common DEGs were identified, among which 12 PR-DEGs were identified, with CASP1, IRF1, NOD2, and PYCARD identified as hub PR-DEGs. These genes were involved in cytokine production, inflammasome activity, necroptosis, NOD-like receptor signaling, and TNF signaling. Immune infiltration analysis showed increased pro-inflammatory immune cell infiltration in JDM patients, with PR-DEGs positively correlated with various immune cell types. GSVA and GSEA analyses demonstrated the involvement of PR-DEGs in multiple inflammation and immunity-related pathways, with the NOD-like receptor signaling pathway playing a central role.
This study highlights the crucial role of pyroptosis in the pathogenesis of JDM, with the identified PR-DEGs potentially contributing to disease development and progression by regulating key inflammatory and immune-related pathways.
青少年皮肌炎（JDM）是一种复杂的自身免疫性疾病，其发病机制仍知之甚少。基于先前对JDM免疫和炎症方面的研究，本研究旨在采用综合生物信息学方法探讨细胞焦亡在JDM发病机制中的作用。
从基因表达综合数据库获得两个微阵列数据集（GSE3307和GSE11971），并编制了一份包含62个细胞焦亡相关基因的列表。进行差异基因表达分析和机器学习分析，以鉴定核心细胞焦亡相关差异表达基因（PR-DEGs）。进行功能富集分析、免疫细胞浸润分析、基因集变异分析（GSVA）和基因集富集分析（GSEA），以阐明PR-DEGs在JDM发病机制中的潜在作用。
共鉴定出2526个常见的差异表达基因，其中12个PR-DEGs被鉴定出来，CASP1、IRF1、NOD2和PYCARD被确定为核心PR-DEGs。这些基因参与细胞因子产生、炎性小体活性、坏死性凋亡、NOD样受体信号传导和TNF信号传导。免疫浸润分析显示JDM患者促炎免疫细胞浸润增加，PR-DEGs与多种免疫细胞类型呈正相关。GSVA和GSEA分析表明PR-DEGs参与多种炎症和免疫相关途径，其中NOD样受体信号通路起核心作用。
本研究强调了细胞焦亡在JDM发病机制中的关键作用，所鉴定的PR-DEGs可能通过调节关键的炎症和免疫相关途径促进疾病的发展和进展。
