Department of Pediatrics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.
Biomed Res Int. 2021 Sep 18;2021:9991726. doi: 10.1155/2021/9991726. eCollection 2021.
Dermatomyositis is an autoimmune disease characterized by severe symmetrical muscle dysfunction and pain. This study was aimed at discovering vital hub genes and potential molecular pathways of DM through bioinformatics analysis, which contributes to identifying potential diagnostic or therapeutic biomarkers and targets. In this study, a total of 915 DEGs in DM samples including 167 upregulated genes and 748 downregulated genes were screened out by the limma package based on the GSE142807 dataset from the Gene Expression Omnibus (GEO) database. Furthermore, the results of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that these downregulated genes were highly associated with the immune-related biological processes and pathways. Therefore, 41 genes closely related to DM were extracted for further study based on the subcluster analysis through the Molecular Complex Detection (MCODE) software plugin in Cytoscape. Ultimately, 10 hub genes (including ISG15, DDX58, IFIT3, CXCL10, and STAT1) were identified as the potential candidate biomarkers and targets. Besides, we found that the identified hub genes directly or indirectly communicated with each other via molecular signaling pathways on the protein and transcription level. In general, under the guidance of bioinformatics analysis, 10 vital hub genes and molecular mechanisms in DM were identified and the expression of proinflammatory factors and interferon family proteins and genes showed high association with DM, which might help provide a theoretical foundation for the development of point-to-point targeted therapy in the future treatment of DM.
皮肌炎是一种自身免疫性疾病,其特征为严重的对称性肌肉功能障碍和疼痛。本研究旨在通过生物信息学分析发现皮肌炎的关键基因和潜在分子通路,有助于鉴定潜在的诊断或治疗生物标志物和靶点。在这项研究中,我们基于基因表达综合数据库(GEO)中的 GSE142807 数据集,使用 limma 软件包筛选出了 915 个 DM 样本中的差异表达基因(DEGs),包括 167 个上调基因和 748 个下调基因。此外,GO 和京都基因与基因组百科全书(KEGG)通路富集分析的结果表明,这些下调基因与免疫相关的生物过程和通路密切相关。因此,我们基于 Cytoscape 中的 Molecular Complex Detection(MCODE)软件插件进行子群分析,提取了 41 个与 DM 密切相关的基因进行进一步研究。最终,我们确定了 10 个关键基因(包括 ISG15、DDX58、IFIT3、CXCL10 和 STAT1)作为潜在的候选生物标志物和靶点。此外,我们发现鉴定出的关键基因在蛋白质和转录水平上通过分子信号通路直接或间接地相互作用。总之,在生物信息学分析的指导下,我们鉴定出了皮肌炎的 10 个关键基因和分子机制,并且促炎因子和干扰素家族蛋白和基因的表达与皮肌炎高度相关,这可能有助于为未来皮肌炎的点对点靶向治疗提供理论基础。