Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China,
Dermatology. 2021;237(3):464-472. doi: 10.1159/000511893. Epub 2020 Dec 10.
Nonsegmental vitiligo (NSV) is an acquired depigmentation disorder of unknown origin. Enormous interests focus on finding novel biomarkers and pathways responsible for NSV.
The gene expression level was obtained by integrating microarray datasets (GSE65127 and GSE75819) from the Gene Expression Omnibus database using the sva R package. Differentially expressed genes (DEGs) between each group were identified by the limma R package. The interaction network was constructed using STRING, and significant modules coupled with hub genes were identified by cytoHubba and molecular complex detection. Pathway analyses were conducted using generally applicable gene set enrichment and further visualized in R environment.
A total of 102 DEGs between vitiligo lesional skin and healthy skin, 14 lesion-specific genes, and 29 predisposing genes were identified from the integrated dataset. Except for the anticipated decrease in melanogenesis, three major functional changes were identified, including oxidative phosphorylation, p53, and peroxisome proliferator-activated receptor (PPAR) signaling in lesional skin. PPARG, MUC1, S100A8, and S100A9 were identified as key hub genes involved in the pathogenesis of vitiligo. Besides, upregulation of the T cell receptor signaling pathway was considered to be associated with susceptibility of the skin in NSV patients.
Our study reveals several potential pathways and related genes involved in NSV using integrated bioinformatics methods. It might provide references for targeted strategies for NSV.
非节段性白癜风（NSV）是一种病因不明的获得性色素减退性疾病。人们对寻找负责 NSV 的新型生物标志物和途径非常感兴趣。
通过整合来自基因表达综合数据库（GSE65127 和 GSE75819）的微阵列数据集，使用 sva R 包获得基因表达水平。通过 limma R 包鉴定各组之间的差异表达基因（DEGs）。使用 STRING 构建互作网络，并通过 cytoHubba 和分子复合物检测鉴定与关键基因耦联的显著模块。使用通用基因集富集进行通路分析，并在 R 环境中进一步可视化。
从整合的数据集中总共鉴定出 102 个 NSV 病变皮肤与健康皮肤之间的差异表达基因、14 个病变特异性基因和 29 个易感性基因。除了预期的黑色素生成减少外，在病变皮肤中还发现了三个主要的功能变化，包括氧化磷酸化、p53 和过氧化物酶体增殖物激活受体（PPAR）信号通路。PPARG、MUC1、S100A8 和 S100A9 被鉴定为涉及白癜风发病机制的关键核心基因。此外，T 细胞受体信号通路的上调被认为与 NSV 患者皮肤的易感性有关。
我们使用整合的生物信息学方法研究揭示了几个可能参与 NSV 的潜在途径和相关基因。它可能为 NSV 的靶向策略提供参考。
