中国组织工程研究2024，Vol.28Issue(27)：4312-4318,7.DOI:10.12307/2024.571
类风湿性关节炎中免疫相关基因表达及免疫细胞的双样本孟德尔随机化分析
Expression of immune-related genes in rheumatoid arthritis and a two-sample Mendelian randomization study of immune cells
摘要
Abstract
BACKGROUND:Rheumatoid arthritis is a chronic systemic autoimmune disease.It is important to study the immunological changes involved in it for diagnosis and treatment. OBJECTIVE:To identify immune-related biomarkers associated with rheumatoid arthritis utilizing bioinformatics techniques and examine alterations in immune cell infiltration as well as the relationship between immune cells and biomarkers. METHODS:Differential expression analysis was used to identify the immune-related genes that were up-regulated in rheumatoid arthritis based on the GEO and Immport databases.Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were used to investigate the possible function of these elevated genes.The immunological characteristic genes associated with rheumatoid arthritis were screened using least absolute shrinkage and selection operator(Lasso)and support vector machine recursive feature elimination(SVM-RFE).Independent datasets were used for difference validation,and the diagnostic performance was evaluated by plotting receiver operating characteristic curves for feature genes.Immune cell infiltration was used to analyze the differential profile of immune cells in rheumatoid arthritis and the correlation between the characterized genes and immune cells.In order to ascertain the causal relationship between monocytes and rheumatoid arthritis in immune cells,Mendelian randomization analysis was ultimately employed. RESULTS AND CONCLUSION:There were 39 upregulated differentially expressed genes in rheumatoid arthritis.The genes were primarily enriched in chemotaxis,cytokine activity,and immune receptor activity,according to GO enrichment analysis,while kEGG enrichment analysis revealed that the genes were considerably enriched in the tumor necrosis factor signaling pathway and peripheral leukocyte migration.Lasso and SVM-RFE identified five feature genes:CXCL13,SDC1,IGLC1,PLXNC1,and SLC29A3.Independent dataset validation of the feature genes found them to be similarly highly expressed in rheumatoid arthritis samples,with area under the curve values greater than 0.8 for all five feature genes in both datasets.Immune cell infiltration indicated that most immune cells,including natural killer cells and monocytes,exhibited increased levels of infiltration in rheumatoid arthritis samples.The correlation analysis revealed a significant positive correlation between memory B cells and immature B cells and these five feature genes.Correlation analysis showed that the five feature genes were positively correlated with memory B cells and immature B cells.The inverse variance weighting method revealed that monocytes were associated with the risk of developing rheumatoid arthritis.关键词
类风湿性关节炎/机器学习/免疫浸润/全基因组关联研究/孟德尔随机化Key words
rheumatoid arthritis/machine learning/immune infiltration/genome-wide association studies/Mendelian randomization分类
医药卫生引用本文复制引用
范以东,秦刚,何凯毅,龚玉芳,李威材,吴广涛..类风湿性关节炎中免疫相关基因表达及免疫细胞的双样本孟德尔随机化分析[J].中国组织工程研究,2024,28(27):4312-4318,7.基金项目
国家自然科学基金(81860793),项目名称:基于IFITM1/Wnt/β-catenin信号通路调控骨肉瘤细胞恶性增殖探讨抑瘤汤抗骨肉瘤的机制,项目负责人:秦刚 （81860793）
国家自然科学基金(82360939),项目名称:circ_CDK14激活miR-520a-3p/SUV39H1诱导骨肉瘤细胞铁死亡及抑瘤汤防治机制研究,项目负责人:秦刚 （82360939）
广西自然科学基金(2020GXNSFAA297140),项目名称:抑瘤汤通过LncRNA MALAT1激活MAPK通路磷酸化抑制骨肉瘤的基础研究,项目负责人:秦刚 （2020GXNSFAA297140）
广西中医药大学2022年研究生教育创新计划项目(YCSY2022028),项目名称:枸杞多糖通过miRNA-20a介导的PTEN/PI3K/AKT信号通路诱导骨肉瘤细胞自噬的机制研究,项目负责人:范以东 National Natural Science Foundation of China,Nos.81860793 and 82360939(both to QG) （YCSY2022028）
Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2020GXNSFAA297140(to QG) （to QG）
Postgraduate Education Innovation Program of Guangxi University of Chinese Medicine in 2022,No.YCSY2022028(to FYD) （to FYD）
