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基于生物信息学探讨类风湿关节炎与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 analysis of rheumatoid arthritis and osteoarthritis based on bioinformatics
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摘要 目的探寻能有效区分类风湿关节炎(RA)和骨关节炎(OA)的潜在生物标志物,并探讨二者在生物信息学方面差异的意义。方法从基因表达综合(GEO)数据库下载2份RA和OA作为相互对照样品的公开可用基因表达谱(GSE55235、GSE55457数据集),并筛选OA与RA的差异表达基因(DEG)。采用LASSO回归模型和SVM-RFE算法识别并筛选生物标志物,在验证组(GSE55584数据集)中进行受试者操作特征(ROC)曲线验证,利用ROC曲线下面积(AUC)值评估辨别能力。利用CIBERSORT算法与筛选出的生物标志物预估RA与OA的生物信息学关联。结果共鉴定出410个DEG,涉及多种信号通路、细胞组分、分子功能和疾病。特征基因有COPZ2、FAH、IL15RA、LTC4S、SCRG1、SFRP1和SLAMF8共7个,且ROC曲线验证结果符合预期。免疫细胞浸润分析显示,巨噬细胞M1、CD8+T细胞、静息肥大细胞、浆细胞、静息树突状细胞等与特征基因相关。结论基于免疫细胞浸润的模型可用于预测RA与OA的鉴别诊断,为RA与OA的治疗靶点提供了新的视角。 Objective To identify the potential biomarkers that could effectively distinguish rheumatoid arthritis(RA)from osteoarthritis(OA)and to explore the significance of bioinformatic differences between the two diseases.Methods Two publicly available gene expression profiles of RA and OA(GSE55235 and GSE55457 datasets)were downloaded from the GEO database and used as mutual control samples.The differentially expressed genes(DEGs)of RA and OA were then screened from the experimental data of 23 RA and 20 OA cases.Moreover,The LASSO regression model and SVM-RFE algorithm were used to identify and screen biomarkers.The ROC curve for the validation group(GSE55584 dataset)was verified,and the area under the ROC curve(AUC)was used to evaluate the discrimination ability.Finally,the CIBERSORT algorithm and selected biomarkers were used to predict the association between RA and OA in bioinformatics.Results Overall,410 DEGs were identified and involved in various signaling pathways,cellular components,molecular functions,and diseases.Furthermore,overall,7 characteristic genes,including COPZ2,FAH,IL15RA,LTC4S,SCRG1,SFRP1,and SLAMF8,were screened by the LASSO regression algorithm and SVM-RFE algorithm and verified by the validation group.The ROC curve verification results were as expected.The immune cell infiltration analysis showed that macrophage M1,CD8+T cells,resting mast cells,plasma cells,and resting dendritic cells were associated with characteristic genes.Conclusion Based on these findings,the immune cell infiltration model can be used to predict the differential diagnosis of RA and OA,and this provides a new perspective for the therapeutic targets for these diseases.
作者 许博 郑福增 刘畅 XU Bo;ZHENG Fuzeng;LIU Chang(Department of Rheumatology,The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450002,China;Department of Rheumatology,Henan Hospital of Traditional Chinese Medicine,Zhengzhou 450002,China)
出处 《中国医科大学学报》 CAS 北大核心 2023年第8期718-723,735,共7页 Journal of China Medical University
基金 河南省中医药科学研究重点课题(2022ZYZD08)。
关键词 类风湿关节炎 骨关节炎 基因本体富集分析 京都基因与基因组数据库富集分析 疾病本体富集分析 免疫细胞浸润分析 rheumatoid arthritis osteoarthritis gene ontology enrichment analysis Kyoto encyclopedia of genes and genomes enrichment analysis disease ontology enrichment analysis immune cell infiltration analysis
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