白斑膏对外阴硬化性苔藓患者全基因表达谱影响的研究

Study on the effect of Baiban Ointment on the whole gene expression profile of vulvar sclerosing lichen

目的:研究白斑膏对外阴硬化性苔藓治疗前后外阴病变组织基因表达谱的影响,并为外阴硬化性苔藓的早期诊断及临床治疗提供理论依据。方法:以病理诊断为外阴硬化性苔藓的患者9例为研究对象,局部外涂白斑膏3个月。应用基因芯片技术,检测患者治疗前后同一部位外阴皮肤组织,并以周边正常处皮肤作为正常对照组,分析基因表达谱的变化,以FC及P值为研究指标,差异表达的标准为FC≥1.5,P<0.05。筛选差异表达基因,并进行GO分析和KEGG数据库基因通路分析。结果:与正常对照组比较,治疗前A组差异表达基因共22个,其中上调21个,下调1个;治疗前A组与治疗后B组比较,差异表达基因23个,均为上调。与白斑膏治疗相关的差异表达基因包括:TBK1、STAT1、ITGAM、VCAN、PRKACB、PROM1、PLAT、SERPINA1。GO分析显示:上调的差异基因主要集中在胞外体,胞浆、细胞外间隙、高尔基体等细胞组分,利用细胞代谢正调控、信号转导调节、细胞黏附等生物过程,起到蛋白结合、酶活性调节等分子功能。KEGG信号通路显示:差异表达基因明显富集于Toll样受体、NOD样受体、FcεRI等信号通路上,均为上调信号通路。其中Toll样受体、NOD样受体信号通路与本病关系最密切。结论:白斑膏对外阴硬化性苔藓治疗,可能是通过调节相关基因的表达,影响Toll样受体等信号通路转导,从而起到调节代谢,炎症和免疫反应等作用,而本研究所筛选出的通路及基因为今后研究本病提供方向。

Objective To study the effect of Baiban Ointment on gene expression profile of vulvar lichen sclerosus before and after treatment,and to provide theoretical basis for the early diagnosis and clinical treatment of vulvar lichen sclerosus.MethodsTotally 9 patients with vulvar lichen sclerosus diagnosed pathologically were selected as the study objects,and the Baiban ointment was applied locally for 3 months.Gene chip technology was used to detect the vulva skin tissue in the same area before and after treatment,and the peripheral normal skin was used as the normal control group to analyze the change of gene expression profile.FC and P values were used as research indicators,and the standard of differential expression was FC value≥1.5,P value<0.05.The differentially expressed genes were screened,and GO analysis and KEGG database gene pathway analysis were carried out.Results Compared with the normal control group,there were 22 differentially expressed genes in Group A before treatment,of which 21 were up-regulated and 1 was down regulated;compared with Group B before treatment,there were 23 differentially expressed genes,all of which were up regulated.The differentially expressed genes related to Baiban ointment treatment included TBK1,STAT1,ITGAM,VCAN,PRKACB,PROM1,PLAT,SERPINA1.Go analysis showed that the up-regulated differential genes were mainly concentrated in the extracellular exosome,cytosol,extracellular space,Golgi apparatus and other cellular component,using the biological process such as positive regulation of cell metabolism,signal transduction regulation,cell adhesion,etc.,to play a role in protein binding,enzyme activity regulation and other molecular functions.KEGG signaling pathway showed that the differentially expressed genes were significantly enriched in Toll like receptor signaling pathway,Nod like receptor signaling pathway and FcεRI signaling pathway,all of which were up-regulated signaling pathways.Among them,Toll like receptor signaling pathway and Nod like receptor signaling pathway were most closely related to the disease.Conclusion Baiban ointment may play a role in regulating metabolism,inflammation and immune response by regulating the expression of related genes,affecting the signal transduction such as Toll like receptor signal pathway.The pathway and the genes screened in this study will provide a direction for the future study of this disease.