散发性前庭神经鞘瘤差异表达基因的鉴定及免疫细胞浸润分析

Identification of Differentially Expressed Genes and Analysis of Immune Cell Infil‐tration in Sporadic Vestibular Schwannoma

目的通过生物信息学方法鉴定散发性前庭神经鞘瘤(vestibular schwannoma,VS)和正常神经组织间的差异表达基因(differentially expressed genes,DEGs)并初步探讨散发性VS中的免疫细胞浸润情况。方法从Gene Expression Omnibus(GEO)数据库中下载散发性VS相关表达谱数据集,利用R软件筛选DEGs,并对DEGs进行基因本体(gene ontology,GO)功能注释和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析。最后通过科学的去卷积算法(CIBERSORT)对散发性VS中22种免疫细胞的浸润情况进行分析。结果共筛选出1828个DEGs,GO分析显示DEGs主要富集在T细胞活化、白血球细胞−细胞粘附以及白细胞、淋巴细胞和单核细胞增生与调控、和细胞因子受体结合。KEGG分析显示DEGs主要富集在细胞因子−细胞因子受体的相互作用、MAPK信号通路、Ras信号通路和细胞粘附分子等通路。免疫细胞浸润分析显示与正常神经组织相比,散发性VS中的M2型巨噬细胞、活化的肥大细胞、未活化的CD4+记忆性T细胞以及嗜酸性粒细胞的比例显著增多(P<0.05);而CD8+T细胞、幼稚CD4+T细胞、调节性T细胞以及中性粒细胞的比例显著减少(P<0.05)。其中M2型巨噬细胞是浸润比例最高的免疫细胞。结论不同的免疫细胞在散发性VS中存在不同的浸润程度,免疫细胞的浸润可能在散发性VS的发生发展中起关键作用。

Objective To identify differentially expressed genes(DEGs)between sporadic schwannoma(VS)and normal neural tissue by bioinformatics methods and discuss infiltration of immune cells in sporadic VS.Methods Data sets of sporadic VS-related expression profiles were downloaded from the Gene Expression Omnibus(GEO)database.DEGs were identified by the R software,and Gene ontology(GO)functional annotation and Kyoto encyclopedia gene and genome(KEGG)pathway analysis were performed on the DEGs.Finally,a scientific deconvolution algorithm(CIBERSORT)was used to analyze infiltration of 22 kinds of immune cells in sporadic VS.Results A total of 1,828 DEGs were identified,enriched mainly in T cell activation,leukocyte cell−cell adhesion,leukocyte and lymphocyte pro-liferation and cytokine receptor binding as shown by GO analysis,and in cytokine−cytokine receptor interaction,MAPK signaling pathway,Ras signaling pathway and cell adhesion molecules by KEGG analysis.Analysis of immune cells infiltration showed significantly increased proportions of M2 macrophages,activated mast cells,resting memory CD4+T cells and eosinophils in sporadic VS as compared with normal nerve tissues(P<0.05),with proportions of CD8+T cells,naive CD4+T cells,regulatory T cells and neutrophils significantly reduced(P<0.05).M2 macrophages were the immune cells with the highest infiltration rate.Conclusion Different immune cells have different levels of infiltration in sporadic VS,and may play a key role in the occurrence and development of sporadic VS.