骨关节炎的氧化应激相关基因和免疫浸润分析  

Analysis of oxidative stress-related genes and immune infiltration in osteoarthritis

作　　者：吴傲 于鹏 滕加文[2] 孔鹏[2] 卞泗善[2] Wu Ao;Yu Peng;Teng Jiawen;Kong Peng;Bian Sishan(The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250000,Shandong Province,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250000,Shandong Province,China)

机构地区：[1]山东中医药大学第一临床医学院,山东省济南市250000 [2]山东中医药大学附属医院,山东省济南市250000

出　　处：《中国组织工程研究》2025年第2期302-311,共10页Chinese Journal of Tissue Engineering Research

摘　　要：背景:目前对于骨关节炎的发病机制尚不清楚,缺乏有效控制疾病的手段,且研究多集中在免疫领域,对氧化应激领域研究较少。目的:探索氧化应激与免疫浸润在骨关节炎中的作用,并预测相关miRNA和治疗药物。方法:从GEO数据库中获取GSE55235数据集(10例骨关节炎样本和10例健康对照样本)和GSE55457数据集(10例骨关节炎样本和10例健康对照样本)进行合并,获取差异表达基因,并结合氧化应激基因得到差异表达氧化应激基因。对差异表达氧化应激基因进行KEGG、GO富集分析,并使用GSEA富集分析评价骨关节炎通路和生物过程。使用STRING在线平台和Cytoscape软件建立了蛋白质相互作用网络,运行Degree算法得到关键基因,从GEO数据库中获取GSE1919作为验证数据集,对关键基因进行差异分析及受试者工作特征曲线分析,得到核心基因。此外,用CIBERSORT对免疫浸润进行评估,并探索核心基因与免疫细胞的相关性,使用TargetScan对核心基因进行miRNA预测及使用DSigDB数据库对靶点药物进行预测。结果与结论:①确定了65个差异表达氧化应激基因和5个核心基因(IL1B、CXCL8、MYC、NFKBIA、JUN);②富集分析结果显示,差异表达氧化应激基因的主要聚焦点包括氧化应激、白细胞介素17、破骨细胞分化、流体剪切应力以及动脉粥样硬化等通路;③5个核心基因的受试者工作特征曲线下面积均>0.85,说明对诊断骨关节具有良好的特异性和敏感性,且与免疫细胞密切关联;④miRNA的预测结果是hsa-miR-3937,治疗小分子药物包括二甲双胍、离子霉素和塞来昔布等。结果表明:骨关节炎中存在氧化应激与免疫浸润,且免疫浸润参与激活氧化应激。核心基因及预测的miRNA可作为诊断骨关节炎的新型标志物,预测的小分子药物可治疗骨关节炎。BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress.OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents.METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software, and the Degree algorithm was run to get the key genes. The GSE1919 dataset was obtained from the GEO database as a validation dataset, and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes. In addition, immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored. miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION: Sixty-five differentially expressed genes and five core genes (IL1B, CXCL8, MYC, NFKBIA, JUN) associated with oxidative stress were identified. Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress, interleukin-17, osteoclast differentiation, fluid shear stress and atherosclerosis. The area under the receiv

关 键 词：骨关节炎 氧化应激 免疫浸润 差异基因 生物标志物 MIRNA 药物预测 

分 类 号：R459.9[医药卫生—治疗学] R34[医药卫生—临床医学] R684.3