Su Mengyun, Shi Ying
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China.
Comb Chem High Throughput Screen. 2025;28(4):615-626. doi: 10.2174/0113862073275508231229112157.
Vitiligo is an autoimmune skin disorder primarily characterized by the absence of melanocytes, leading to the development of white patches on the patient's skin. Narrowband Ultraviolet B (NB-UVB) therapy is among the most effective approaches for stimulating the reformation of hyperpigmentation. This treatment utilizes a narrow spectrum of NBUVB wavelengths ranging from 311 to 313 nm to irradiate the affected area, thereby preventing the destruction of migrating and proliferating melanocytes. Nevertheless, the molecular alterations occurring in both the hair follicle and the interfollicular epidermis during NB-UVB treatment remain unknown.
In this study, we conducted a comprehensive analysis of the consistency of differentially expressed genes (DEGs) within the enrichment pathways both before and after NB-UVB treatment, utilizing a bioinformatics approach. Furthermore, we employed CYTOHUBBA and Random Forest algorithms to identify and sequence hub genes from the pool of DEGs. Following validation of these hub genes through ROC curve analysis, we proceeded to construct an interaction network between these hub genes, miRNA, and drugs. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to further verify the difference in the expression of hub genes between the disease group and the control group.
Gene Set Enrichment Analysis of DEGs indicated strong associations with vitiligo in most pathways. Subsequently, we conducted Gene Ontology and Metascape enrichment analyses on the overlapping genes from DEGs. We identified key genes (COL11A1, IGFBP7, LOX, NTRK2, SDC2, SEMA4D, and VEGFA) within the Protein-Protein Interaction (PPI) network. We further explored potential drugs that could be used for the clinical treatment of vitiligo through the drug-hub gene interaction network. Finally, the results of RT-qPCR experiments demonstrated that the expression levels of the identified hub genes in both groups were consistent with the bioinformatics analysis results.
The hub genes obtained in this study may be a biomarker related to the development of vitiligo pigmentation. Our research not only contributes to a better understanding of the treatment mechanisms of vitiligo but also provides valuable insights for future personalized medical approaches and targeted therapies for vitiligo.
白癜风是一种自身免疫性皮肤病,主要特征是缺乏黑素细胞,导致患者皮肤出现白色斑块。窄谱中波紫外线(NB-UVB)疗法是刺激色素沉着重新形成的最有效方法之一。这种治疗利用311至313nm的窄谱NBUVB波长照射受影响区域,从而防止迁移和增殖的黑素细胞被破坏。然而,NB-UVB治疗期间毛囊和毛囊间表皮中发生的分子变化仍然未知。
在本研究中,我们利用生物信息学方法对NB-UVB治疗前后富集通路内差异表达基因(DEG)的一致性进行了全面分析。此外,我们使用CYTOHUBBA和随机森林算法从DEG库中识别并排序枢纽基因。通过ROC曲线分析验证这些枢纽基因后,我们构建了这些枢纽基因、miRNA和药物之间的相互作用网络。实时定量聚合酶链反应(RT-qPCR)用于进一步验证疾病组和对照组之间枢纽基因表达的差异。
DEG的基因集富集分析表明,大多数通路与白癜风有很强的关联。随后,我们对DEG的重叠基因进行了基因本体论和Metascape富集分析。我们在蛋白质-蛋白质相互作用(PPI)网络中确定了关键基因(COL11A1、IGFBP7、LOX、NTRK2、SDC2、SEMA4D和VEGFA)。我们通过药物-枢纽基因相互作用网络进一步探索了可用于白癜风临床治疗的潜在药物。最后,RT-qPCR实验结果表明,两组中鉴定出的枢纽基因的表达水平与生物信息学分析结果一致。
本研究中获得的枢纽基因可能是与白癜风色素沉着发展相关的生物标志物。我们的研究不仅有助于更好地理解白癜风的治疗机制,还为未来白癜风的个性化医疗方法和靶向治疗提供了有价值的见解。