Department of Rheumatology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China.
J Dermatol. 2021 Jul;48(7):1007-1020. doi: 10.1111/1346-8138.15856. Epub 2021 Apr 23.
Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. The pathogenic mechanisms remain ill-defined. The purpose of this study was to identify key genes related to JDM. Microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEG) were identified. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction (PPI) network were carried out. In addition, the hub genes were selected by cytoHubba. The expression profile and diagnostic capacity (receiver-operator curve [ROC]) of interested hub genes were verified. Gene set enrichment analysis (GSEA) was also carried out. Moreover, the signature of hub genes was then used as a search query to explore the Connectivity Map (CMAP). A total of 128 DEG were identified. The enriched functions and pathways of the DEG include response to virus, negative regulation of cell migration, cadmium ion transmembrane transport, defense response to Gram-negative bacterium, positive regulation of megakaryocyte differentiation, and negative regulation of angiogenesis. Twenty-one hub genes were identified. The expression levels of the interested genes were also confirmed. ROC analysis confirmed that the expression of these genes can distinguish JDM from controls. GSEA showed that these genes are mainly related to "inflammatory response", "complement", "interferon-α response", "IL6/JAK/STAT3 signaling", "TGF-β signaling", "IL2/STAT5 signaling" and "TNF-α signaling via NF-κB". The CMAP research found some compounds with the potential to counteract the effects of the dysregulated molecular signature in JDM. In this study, bioinformatics methods were used to identify DEG, which helps us understand the molecular mechanisms of JDM and provide candidate targets for diagnosis and treatment of JDM.
幼年特发性关节炎（JDM）是一种慢性自身免疫性疾病。其发病机制仍不明确。本研究旨在鉴定与 JDM 相关的关键基因。从基因表达综合数据库中下载微阵列数据集。鉴定差异表达基因（DEG）。然后进行基因本体论、京都基因与基因组百科全书通路富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。此外，通过 cytoHubba 选择枢纽基因。验证感兴趣的枢纽基因的表达谱和诊断能力（接收者操作特征曲线[ROC]）。还进行了基因集富集分析（GSEA）。此外，还将枢纽基因的特征用作搜索查询来探索连接图谱（CMAP）。共鉴定出 128 个 DEG。DEG 的富集功能和通路包括对病毒的反应、细胞迁移的负调控、镉离子跨膜转运、对革兰氏阴性菌的防御反应、巨核细胞分化的正调控和血管生成的负调控。鉴定出 21 个枢纽基因。感兴趣基因的表达水平也得到了确认。ROC 分析证实，这些基因的表达可以区分 JDM 和对照。GSEA 表明，这些基因主要与“炎症反应”、“补体”、“干扰素-α反应”、“IL6/JAK/STAT3 信号”、“TGF-β信号”、“IL2/STAT5 信号”和“TNF-α信号通过 NF-κB”有关。CMAP 研究发现了一些具有潜在作用的化合物，可以对抗 JDM 中失调分子特征的作用。在这项研究中，使用了生物信息学方法来鉴定 DEG，这有助于我们理解 JDM 的分子机制，并为 JDM 的诊断和治疗提供候选靶点。
