银屑病皮损核心基因筛选及其潜在免疫机制探索  

Screening of hub genes in skin lesions of psoriasis and exploration of potential immune mechanisms

作　　者：雷明君 李文雪 赵军 白帆 LEI Ming-jun;LI Wen-xue;ZHAO Jun;BAI Fan(The First Department of Dermatology,the First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050013,China)

机构地区：[1]河北中医药大学第一附属医院皮肤一科,河北石家庄050013

出　　处：《河北医科大学学报》2023年第12期1393-1399,共7页Journal of Hebei Medical University

基　　金：河北省医学科学研究课题计划(2020032)。

摘　　要：目的旨在通过机器学习算法筛选银屑病致病核心基因,以及探索潜在的免疫细胞亚型招募机制。方法从公共数据库下载银屑病皮损组织样本(lesional sample,LS)(n=44)和非皮损组织样本(non-lesional sample,NLS)(n=44)全转录组测序数据(GSE142582、GSE161683、GSE121212)。筛选LS和NLS差异表达基因(differentially expressed genes,DEGs)。使用机器学习算法筛选核心基因。使用ssGSEA算法计算样本中免疫细胞浸润含量。分析核心基因表达量与免疫细胞亚型浸润含量之间的相关性。结果本研究筛选出DEGs 151个。通过WGCNA和Lasso回归分析共同确定核心基因4个,分别是CCL20、TNFRSF17、ALDH3A1和EPN3。CCL20和TNFRSF17正向调控银屑病皮损样本免疫细胞浸润,ALDH3A1和EPN3负向调控银屑病皮损样本免疫细胞浸润。结论4个基因即CCL20、ALDH3A1、EPN3和TNFRSF17,对银屑病皮损具有较好的诊断效能。CCL20和TNFRSF17与银屑病皮损样本免疫细胞浸润含量正相关,可能招募免疫细胞富集。而ALDH3A1和EPN3可能负向调控免疫反应,对皮肤起到保护作用。CCL20、ALDH3A1、EPN3和TNFRSF17可能成为银屑病潜在的生物学标志和治疗靶点。Objective To screen the pathogenic hub genes of psoriasis by machine learning algorithm and to explore the potential mechanism of immune cell subtype recruitment.Methods Transcriptome sequencing data sets of psoriasis lesional samples(LS)(n=44)and non-lesional tissue samples(NLS)(n=44)were downloaded from public database(GSE142582,GSE161683 GSE121212).We screened differentially expressed genes(DEGs)between LS and NLS.The machine learning algorithm was applied to screen the hub genes,and ssGSEA was used to calculate the immune cell infiltration(ICI)level in the samples.The correlation between hub genes expression level and ICI level was analyzed.Results A total of 151 DEGs were screened out in this study.Four hub genes were identified by WGCNA and LASSO regression analysis,which were CCL20,TNFRSF17,ALDH3A1 and EPN3.The four genes had good diagnostic efficacy.CCL20 and TNFRSF17 positively regulated the ICI in LS,while ALDH3A1 and EPN3 negatively regulated ICI in NLS.Conclusion Four genes,including CCL20,ALDH3A1,EPN3 and TNFRSF17,have good diagnostic efficacy in psoriasis lesions.CCL20 and TNFRSF17 are positively correlated with ICI level in LS,which may recruit immune cells.However,ALDH3A1 and EPN3 may negatively regulate immune response and play a protective role in skin.CCL20,ALDH3A1,EPN3 and TNFRSF17 may be the potential biomarkers and therapeutic targets of psoriasis.

关 键 词：银屑病 TH17细胞 核心基因 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]