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盘状红斑狼疮皮肤活检关键生物标志物的生物信息学分析及免疫浸润

Bioinformatic analysis of key biomarkers and immune filtration of skin biopsy in discoid lupus erythematosus.

作者信息

Xiang Mengmeng, Chen Qian, Feng Yang, Wang Yilun, Wang Jie, Liang Jun, Xu Jinhua

机构信息

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Cutaneous Biology Research Center & Melanoma Program MGH Cancer Center, Harvard Medical School/Massachusetts General Hospital, Boston, MA, USA.

出版信息

Lupus. 2021 Apr;30(5):807-817. doi: 10.1177/0961203321992434. Epub 2021 Feb 2.

Abstract

OBJECTIVE

Discoid lupus erythematosus (DLE) is the most common category of chronic cutaneous lupus erythematosus, where the pathological process is proved to be closely associated with immunity. This bioinformatic analysis sought to identify key biomarkers and to perform immune infiltration analysis in the skin biopsy samples of DLE.

METHODS

GSE120809, GSE100093, GSE72535, GSE81071 were used as the data source of gene expression profiles, altogether containing 79 DLE samples and 47 normal controls (NC). Limma package was applied to identify differentially expressed genes (DEGs) and additional Gene Ontology (GO) together with The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were done. Protein-protein interaction network (PPI) was constructed using STRING and Cytoscape. Hub genes were selected by CytoHubba. Finally, immune filtration analysis was finished by the CIBERSORT algorithm, and comparisons between the two groups were accomplished.

RESULTS

A total of 391 DEGs were identified, which were composed of 57 up-regulated genes and 334 down-regulated genes. GO and KEGG enrichment analyses revealed that DEGs were closely related with different steps in the immune response. Top 10 hub genes included GBP2, HLA-F, IFIT2, RSAD2, ISG15, IFIT1, IFIT3, MX1, XAF1 and IFI6. Immune filtration analysis from CIBERSORT had found that compared with NC, DLE samples had higher percentages of CD8+ T cells, T cells CD4 memory activated, T cells gamma delta, macrophages M1 and lower percentages of T cells regulatory, macrophages M2, dendritic cells resting, mast cells resting, mast cells activated.

CONCLUSION

This bioinformatic study selected key biomarkers from the contrast between DLE and NC skin samples and is the first research to analyze immune cell filtration in DLE.

摘要

目的

盘状红斑狼疮(DLE)是慢性皮肤型红斑狼疮最常见的类型,其病理过程被证明与免疫密切相关。本生物信息学分析旨在鉴定关键生物标志物,并对DLE皮肤活检样本进行免疫浸润分析。

方法

使用GSE120809、GSE100093、GSE72535、GSE81071作为基因表达谱的数据源,共包含79个DLE样本和47个正常对照(NC)。应用Limma软件包鉴定差异表达基因(DEG),并进行额外的基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用STRING和Cytoscape构建蛋白质-蛋白质相互作用网络(PPI)。通过CytoHubba选择枢纽基因。最后,通过CIBERSORT算法完成免疫过滤分析,并对两组进行比较。

结果

共鉴定出391个DEG,其中包括57个上调基因和334个下调基因。GO和KEGG富集分析表明,DEG与免疫反应的不同步骤密切相关。前10个枢纽基因包括GBP2、HLA-F、IFIT2、RSAD2、ISG15、IFIT1、IFIT3、MX1、XAF1和IFI6。来自CIBERSORT的免疫过滤分析发现,与NC相比,DLE样本中CD8 + T细胞、CD4记忆活化T细胞、γδ T细胞、M1巨噬细胞的百分比更高,而调节性T细胞、M2巨噬细胞、静息树突状细胞、静息肥大细胞、活化肥大细胞的百分比更低。

结论

本生物信息学研究从DLE和NC皮肤样本的对比中筛选出关键生物标志物,是首次对DLE进行免疫细胞过滤分析的研究。

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