Nanyang Medical College, Henan, 473000, China.
Sci Rep. 2023 Mar 18;13(1):4508. doi: 10.1038/s41598-023-31438-6.
Studies have implicated necroptosis mechanisms in orthopaedic-related diseases, since necroptosis is a unique regulatory cell death pattern. However, the role of Necroptosis-related genes in rheumatoid arthritis (RA) has not been well described. We downloaded RA-related data information and Necroptosis-related genes from the Gene Expression Omnibus (GEO), Kyoto Gene and Genome Encyclopedia (KEGG) database, and Genome Enrichment Analysis (GSEA), respectively. We identified 113 genes associated with RA-related necroptosis, which was closely associated with the cytokine-mediated signaling pathway, necroptosis and programmed necrosis. Subsequently, FAS, MAPK8 and TNFSF10 were identified as key genes among 48 Necroptosis-associated differential genes by three machine learning algorithms (LASSO, RF and SVM-RFE), and the key genes had good diagnostic power in distinguishing RA patients from healthy controls. According to functional enrichment analysis, these genes may regulate multiple pathways, such as B-cell receptor signaling, T-cell receptor signaling pathways, chemokine signaling pathways and cytokine-cytokine receptor interactions, and play corresponding roles in RA. Furthermore, we predicted 48 targeted drugs against key genes and 31 chemical structural formulae based on targeted drug prediction. Moreover, key genes were associated with complex regulatory relationships in the ceRNA network. According to CIBERSORT analysis, FAS, MAPK8 and TNFSF10 may be associated with changes in the immune microenvironment of RA patients. Our study developed a diagnostic validity and provided insight to the mechanisms of RA. Further studies will be required to test its diagnostic value for RA before it can be implemented in clinical practice.
研究表明坏死性凋亡机制与骨科相关疾病有关，因为坏死性凋亡是一种独特的调节性细胞死亡模式。然而，坏死相关基因在类风湿关节炎（RA）中的作用尚未得到很好的描述。我们分别从基因表达综合数据库（GEO）、京都基因与基因组百科全书（KEGG）数据库和基因组富集分析（GSEA）下载了与 RA 相关的坏死性凋亡相关数据信息和基因。我们确定了 113 个与 RA 相关的坏死性凋亡相关基因，这些基因与细胞因子介导的信号通路、坏死性凋亡和程序性细胞坏死密切相关。随后，通过三种机器学习算法（LASSO、RF 和 SVM-RFE），我们从 48 个与坏死性凋亡相关的差异基因中确定了 FAS、MAPK8 和 TNFSF10 为关键基因，这些关键基因在区分 RA 患者和健康对照者方面具有良好的诊断能力。根据功能富集分析，这些基因可能调节多种途径，如 B 细胞受体信号、T 细胞受体信号通路、趋化因子信号通路和细胞因子-细胞因子受体相互作用，并在 RA 中发挥相应作用。此外，我们基于靶向药物预测，预测了针对关键基因的 48 种靶向药物和 31 种化学结构式。此外，关键基因在 ceRNA 网络中存在复杂的调控关系。根据 CIBERSORT 分析，FAS、MAPK8 和 TNFSF10 可能与 RA 患者免疫微环境的变化有关。我们的研究开发了一种诊断有效性，并为 RA 的发病机制提供了新的见解。在将其应用于临床实践之前，还需要进一步的研究来检验其对 RA 的诊断价值。
