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生物信息学分析类风湿关节炎的关键生物标志物和免疫浸润
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Abstract:
目的：挖掘类风湿关节炎的潜在基因标志物，探究类风湿关节炎的免疫浸润情况，为进一步阐明类风湿关节炎的发生发展提供方向，并指导临床治疗。方法：从基因表达综合数据库(GEO)下载GSE55235基因集，获得RA和健康样本之间的差异表达基因(DEGs)。用R软件进行DEGs的基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。我们还进行基因集富集分析(GSEA)以进一步了解基因的功能，并利用加权基因共表达网络分析(WGCNA)构建基因共表达网络，并确定最重要的模块。并运用Cytoscape软件构建蛋白互作网络，筛选出位于Top 5的关键基因。建立临床预测模型对得到的关键基因进行验证。最后，使用R软件的“e1071”,“CIBERSORT”和“parallel”包来分析疾病的免疫细胞浸润模式。结果：总共筛选了5个在RA的发生发展中最具重要意义差异基因(IGLJ3、IGHM、IGKC、IGLV1-44、GUSBP11)。生物功能分析确定了RA中的关键相关通路、基因模块和共表达网络。免疫浸润分析发现，CD8阳性T淋巴细胞和浆细胞浸润增加，CD4阳性的静息记忆T淋巴细胞和活性肥大细胞浸润减少可能与RA的发生有关。结论：IGLJ3、IGHM、IGKC、IGLV1-44、GUSBP11基因在RA的发生发展中具有重要作用，这将有助于确定RA的新型诊断标志物和治疗靶点，也为后续的发病机制研究提供可靠的依据和全新的视角。
Objective: Excavate the potential gene markers of rheumatoid arthritis and explore the immune in-filtration of rheumatoid arthritis, so as to provide direction for further clarifying the occurrence and development of rheumatoid arthritis and guide clinical treatment. Methods: The GSE55235 gene set was downloaded from the Gene Expression Omnibus data base (GEO), and the differentially ex-pressed genes (DEGs) between RA and healthy samples were obtained. The Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by R software. We performed Gene Set Enrichment Analysis (GSEA) to further understand the func-tions of the hub gene. Weighted gene co-expression network analysis (WGCNA) would be utilized to build a gene co-expression network, and the most significant module and hub genes were identified. The protein interaction network was constructed by using Cytoscape software to screen the key genes in the top 5. A clinical prediction model is established to verify the keygenes. e1071, CIBERSORT, parallel package of R software are helpful to analyze the immune cell infiltration pat-tern of disease. Results: A total of 5 main differential genes (IGLJ3, IGHM, IGKC, IGLV1-44, GUSBP11) were screened. Biological function analysis identified the key related pathways, gene modules and coexpression networks in RA. Immune infiltration analysis showed that plasma cell and CD8 posi-tive T cells infiltration increased and CD4 positive T cell and Mast cells activated infiltration de-creased, which may be related to the occurrence of RA. Conclusion: IGLJ3, IGHM, IGKC, IGLV1-44, GUSBP11 genes play an important role in the occurrence and development of RA, which will help to determine the new diagnostic markers and therapeutic targets of RA, and also provide a reliable basis and a new perspective for the follow-up pathogenesis research.
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