【摘要】 目的 基于生物信息学和机器学习方法探讨类风湿性关节炎(RA)和强直性脊柱炎(AS)潜在的核心基因与共享分子机制。方法 本研究从基因表达数据库(GEO)获取RA和AS的基因表达数据，并利用R软件包进行差异表达基因(DEGs)分析。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析探索共表达DEGs的生物学功能。利用蛋白质-蛋白质相互作用(PPI)网络和机器学习算法筛选核心基因，并构建列线图对核心基因进行验证。使用基因集富集分析(GSEA)以及免疫细胞浸润分析研究与核心基因相关的分子途径和免疫细胞分布。利用药物预测和分子对接筛选RA与AS潜在的共同靶向药物。结果 本研究共筛选出47个上调和23个下调的共表达DEGs,涉及通路主要有Th1和Th2细胞分化通路等。在共表达DEGs中，筛选并验证了2个核心基因，即白细胞介素2受体β亚基(IL2RB)及runt相关转录因子3(RUNX3)。受试者工作特征(ROC)曲线分析显示，IL2RB和RUNX3在验证集中均具有良好的诊断效能(曲线下面积>0.7)。免疫浸润分析强调中性粒细胞及CD8~+ T细胞在RA与AS发病机制中的重要作用。药物预测与分子对接结果表明，维A酸可通过靶向核心基因参与RA与AS共同病理过程，为后续机制研究和治疗靶点验证提供线索。结论 Th1/Th2细胞分化通路是RA-AS共享的核心机制，核心基因IL2RB、RUNX3可能通过调控该通路及免疫细胞功能参与RA和AS共同发生发展。更多还原

【Abstract】 Objective To explore the potential core genes and shared molecular mechanisms of rheumatoid arthritis(RA) and ankylosing spondylitis(AS) based on bioinformatics and machine learning methods. Methods Gene expression data for RA and AS were obtained from the Gene Expression Omnibus(GEO) database, and differential expression genes(DEGs) analysis was performed using R software packages. The biological functions of the co-expressed DEGs were explored through Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Protein-protein interaction(PPI) networks and machine learning algorithms were employed to screen for core genes, and nomograms were constructed to validate these core genes. Gene set enrichment analysis(GSEA) and immune cell infiltration analysis were utilized to investigate the molecular pathways and immune cell distributions associated with the core genes. Potential common targeted drugs for RA and AS were screened using drug prediction and molecular docking. Results A total of 47 upregulated and 23 downregulated co-expressed DEGs were identified in this study,primarily involving pathways such as the Th1 and Th2 cell differentiation pathways. Among the co-expressed DEGs,two core genes,namely interleukin 2 receptor subunit beta(IL2RB) and runt-related transcription factor 3(RUNX3),were screened and validated. Receiver operating characteristic(ROC) curve analysis demonstrated that both IL2RB and RUNX3 exhibited good diagnostic performance in the validation set(the area under the curve > 0. 7). Immune infiltration analysis highlighted the significant roles of neutrophils and CD8~+ T cells in the pathogenesis of RA and AS. Drug prediction and molecular docking results indicated that retinoic acid could participate in the common pathological processes of RA and AS by targeting core genes,providing clues for subsequent mechanistic research and therapeutic target validation. Conclusion Th1/Th2 cell differentiation pathway is a core mechanism shared by RA and AS,and the core genes IL2RB and RUNX3 may be involved in the co-occurrence and progression of RA and AS by regulating this pathway and immune cell functions.更多还原