基于生物信息学方法探讨银屑病关键差异基因的免疫浸润机制及相关中药预测分析

Bioinformatics Based Study on Immune Infiltration Mechanism of Psoriasis Pivotal Differential Genes and Prediction of Related Traditional Chinese Medicine

目的探讨银屑病关键差异基因的免疫浸润机制及分析预测相关作用中药。方法利用基因芯片数据库(Gene Expression Omnibus,GEO),对银屑病基因探针芯片数据进行富集分析和免疫浸润分析。运用R语言及相关安装包程序对银屑病差异基因进行基因本体论(GO)及基因通路富集分析(KEGG);通过CIBERSORT反卷法对22类免疫细胞在银屑病的含量及比例进行分析;利用COREMINE数据库对明显富集的免疫相关的生物学过程及核心靶基因进行中药预测。结果银屑病相关的蛋白网络互作关键靶基因涉及KIF2C、BUB1、BUB1B等14个靶基因,涉及中性粒细胞活化、淋巴细胞迁移、白细胞趋化性等多种免疫相关途径,与自身免疫、炎症、心肌代谢通路密切相关。CIBERSORT反卷积法对银屑病的免疫相关性分析中,调节性T细胞、活化的树突状细胞与活化的CD4^(+)记忆性T细胞呈正相关,而活化的树突状细胞与静息肥大细胞、巨噬细胞M2呈负相关。在总体样本中,与正常皮肤组织组相比,银屑病皮损组织中中性粒细胞、活化的树突状细胞、静息的CD4^(+)记忆T细胞明显增高,而静息肥大细胞则明显减少,而在配对样本中记忆B细胞在银屑病组织中呈现上升趋势,而调节性T细胞呈下降趋势。免疫相关性分析中,调节性T细胞、活化的树突状细胞与活化的CD4^(+)记忆性T细胞呈正相关,而活化的树突状细胞与静息肥大细胞、巨噬细胞M2呈负相关。通过COREMINE预测发现,半枝莲、白花蛇舌草、人参、黄芪、防己与银屑病相关免疫浸润的关系最密切,且多归为肺经,功效多与清热补虚相关。结论中性粒细胞、树突状细胞、CD4^(+)记忆T细胞、调节性T细胞与银屑病关系密切,银屑病相关的差异基因涉及多种免疫相关生物学过程及通路,筛选出半枝莲、白花蛇舌草、人参、黄芪、防己等中药可能为其潜在的分子药物来源。

Objective To explore the immune infiltration mechanism of key differential genes in psoriasis,and predict Chinese herbs for the treatment of psoriasis.Methods The data of the psoriatic gene probe microarray was enriched and analyzed by Gene Expression Omnibus(GEO).The gene ontology(GO)and gene pathway enrichment analysis(KEGG) of psoriasis differential genes were performed by R language and related installation package program.CIBERSORT method was used to analyze the content and proportion of 22 kinds of immune cells in psoriasis.COREMINE database was used to predict Chinese herbs related to the immune-related biological processes and core target genes.Results 14 target genes,including KIF2 C,BUB1 and BUB1 B,are involved in psoriasisrelated protein network interaction hub.Many immune-related biological processes,such as neutrophil activation,lymphocyte migration and leukocyte chemotaxis,are likely to be involved.It is closely related to autoimmune,inflammatory and myocardial metabolic pathways.The results of immune correlation of psoriasis by CIBERSORT deconvolution method suggested that regulatory T cells,activated dendritic cells were positively correlated with activated CD4^(+) memory T cells,while activated dendritic cells were negatively correlated with resting mast cells and macrophages M2.Compared with normal skin tissue,neutrophils,activated dendritic cells and resting CD4^(+) memory T cells were significantly increased in psoriatic lesions,while resting mast cells were significantly decreased.In paired samples,memory B cells showed an upward trend,regulatory T cells showed a downward trend.In immunocorrelation analysis,regulatory T cells and activated dendritic cells were positively correlated with activated CD4^(+) memory T cells,while activated dendritic cells were negatively correlated with resting mast cells and macrophage M2.COREMINE showed that Scutellaria barbata,Hedyotis diffusa,ginseng,Astragalus membranaceus and Fangji had the closest relationship with psoriasis-related immune infiltration,and most of them belonged to lung meridian,and the efficacy was related to clearing heat and tonifying deficiency.Conclusion Neutrophils,dendritic cells,CD4^(+) memory T cells and regulatory T cells are closely related to psoriasis.Psoriasis-related differential genes are involved in a variety of immune-related biological processes and pathways.Scutellaria barbata,Hedyotis diffusa,ginseng,Astragalus membranaceus,Fangji and other traditional Chinese medicine may be selected as potential molecular drug sources.