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基于生物信息学探讨骨关节炎相关分子机制及免疫细胞浸润分析 被引量:1

Molecular mechanism and immune cell infiltration of osteoarthritis based on bioinformatics
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摘要 目的利用生物信息学技术探讨骨关节炎发病的相关分子机制。方法通过基因表达综合(GEO)数据库获取2份骨关节炎芯片(GSE51588、GSE98918)作为对照样品组,并筛选出骨关节炎与正常对照组的差异表达基因,对其行基因本体(GO)和疾病本体(DO)富集分析。通过LASSO回归模型和SVM-RFE算法识别筛选生物标志物,在验证组GSE117999芯片中行受试者操作特征(ROC)曲线验证,再利用ROC曲线下面积值评估辨别能力。利用CIBERSORT算法预估骨关节炎与筛选出的生物标志物的生物信息学关联。结果共鉴定出骨关节炎差异基因96个,其中上调、下调基因分别为47、49个,GO和DO富集分析涉及多种信号通路、细胞组分、分子功能和疾病。LASSO回归算法和SVM-RFE算法筛选并经过验证组验证后得到的特征基因为CSN1S1、CXCL14、MTHFD2、NMNAT2、TLR7,且ROC曲线验证结果符合预期。免疫细胞浸润分析显示,正常对照组幼稚B细胞、单核细胞、激活的肥大细胞、中性粒细胞相对含量明显增加,而骨关节炎组幼稚CD4^(+)T细胞、滤泡辅助细胞、巨噬细胞M1、静息树突状细胞相对含量明显增加;特征基因与单核细胞、巨噬细胞M1、浆细胞、CD8^(+)T细胞、幼稚B细胞、调节性T细胞、静息肥大细胞等相关。结论基于免疫细胞浸润的模型可用于预测骨关节炎的发病机制,为骨关节炎治疗提供新靶点。 Objective To explore the molecular mechanism of osteoarthritis using bioinformatics technology.Methods Two osteoarthritis microarrays,GSE51588 and GSE98918 microarrays,were obtained from the GEO database as the control sample group,and the differentially expressed genes between the osteoarthritis and normal control group were screened.Subsequently,the differentially expressed genes were analyzed for gene ontology(GO)and disease ontology(DO)enrichment.The biomarkers were identified and screened using the LASSO regression model and SVM-RFE algorithm.Then,the ROC curve was verified in the GSE117999 chip of the verification group,and the area under the ROC curve was used to evaluate the discrimination ability.Finally,the CIBERSORT algorithm was used to predict the bioinformatics association between the selected biomarkers and osteoarthritis.Results A total of 96 differentially expressed genes were identified,including 47 and 49 genes with upregulated and downregulated expression,respectively.The enrichment analysis of the identified differential genes GO and DO involved diverse signaling pathways,cellular components,molecular functions,and diseases.The characteristic genes screened using the LASSO regression algorithm and SVM-RFE algorithm and verified by the verification group included CSN1S1,CXCL14,MTHFD2,NMNAT2,and TLR7;thus,the ROC curve verification results were in line with expectations.Immune cell infiltration analysis showed that the relative contents of naive B cells,monocytes,activated mast cells,and neutrophils were significantly increased in the normal group,while the relative contents of naive CD4^(+)T cells,follicular helper cells,macrophage M1,and resting dendritic cells were significantly increased in the osteoarthritis group.Characteristic genes were associated with monocytes,macrophage M1,plasma cells,CD8^(+)T cells,naive B cells,regulatory T cells,resting mast cells,among others.Conclusion The model based on immune cell infiltration can be used to predict the pathogenesis of osteoarthritis and provide a potential therapeutic target for treatment of osteoarthritis.
作者 刘畅 卞华 许博 LIU Chang;BIAN Hua;XU Bo(Department of Rheumatology,Henan Province Hospital of TCM,The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450002,China;Zhang Zhongjing College of Traditional Chinese Medicine,Nanyang Institute of Technology,Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Nanyang 473004,China)
出处 《中国医科大学学报》 CAS 北大核心 2023年第5期385-391,397,共8页 Journal of China Medical University
基金 国家自然科学基金(82074415)。
关键词 骨关节炎 发病机制 免疫细胞浸润分析 osteoarthritis pathogenesis analysis of immune cell infiltration
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