Department of Orthopaedics, Hangzhou Ninth People's Hospital, Hangzhou, Zhejiang, China.
Department of Orthopaedics, The First Affiliated Hospital of Zhejiang University of Chinese Medicine, Hangzhou, China.
Front Endocrinol (Lausanne). 2023 Mar 15;14:1144250. doi: 10.3389/fendo.2023.1144250. eCollection 2023.
Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, is often characterized by persistent morning stiffness, joint pain, and swelling. Early diagnosis and timely treatment of RA can effectively delay the progression of the condition and significantly reduce the incidence of disability. In the study, we explored the function of pyroptosis-related genes (PRGs) in the diagnosis and classification of rheumatoid arthritis based on Gene Expression Omnibus (GEO) datasets.
We downloaded the GSE93272 dataset from the GEO database, which contains 35 healthy controls and 67 RA patients. Firstly, the GSE93272 was normalized by the R software "limma" package. Then, we screened PRGs by SVM-RFE, LASSO, and RF algorithms. To further investigate the prevalence of RA, we established a nomogram model. Besides, we grouped gene expression profiles into two clusters and explored their relationship with infiltrating immune cells. Finally, we analyzed the relationship between the two clusters and the cytokines.
CHMP3, TP53, AIM2, NLRP1, and PLCG1 were identified as PRGs. The nomogram model revealed that decision-making based on established model might be beneficial for RA patients, and the predictive power of the nomogram model was significant. In addition, we identified two different pyroptosis patterns (pyroptosis clusters A and B) based on the 5 PRGs. We found that eosinophil, gamma delta T cell, macrophage, natural killer cell, regulatory T cell, type 17 T helper cell, and type 2 T helper cell were significant high expressed in cluster B. And, we identified gene clusters A and B based on 56 differentially expressed genes (DEGs) between pyroptosis cluster A and B. And we calculated the pyroptosis score for each sample to quantify the different patterns. The patients in pyroptosis cluster B or gene cluster B had higher pyroptosis scores than those in pyroptosis cluster A or gene cluster A.
In summary, PRGs play vital roles in the development and occurrence of RA. Our findings might provide novel views for the immunotherapy strategies with RA.
类风湿关节炎（RA）是一种慢性自身免疫性炎症性疾病，常表现为持续晨僵、关节疼痛和肿胀。早期诊断和及时治疗 RA 可以有效延缓病情进展，显著降低残疾发生率。本研究基于基因表达综合数据库（GEO）数据集，探讨了焦亡相关基因（PRGs）在类风湿关节炎诊断和分类中的作用。
从 GEO 数据库中下载 GSE93272 数据集，该数据集包含 35 名健康对照者和 67 名 RA 患者。首先，使用 R 软件“limma”包对 GSE93272 进行标准化。然后，采用 SVM-RFE、LASSO 和 RF 算法筛选 PRGs。为进一步探讨 RA 的发病情况，建立了列线图模型。此外，我们将基因表达谱分为两个聚类，并探讨了它们与浸润免疫细胞的关系。最后，分析了两个聚类与细胞因子的关系。
鉴定出 CHMP3、TP53、AIM2、NLRP1 和 PLCG1 为 PRGs。列线图模型表明，基于建立的模型进行决策可能对 RA 患者有益，且该模型的预测能力具有统计学意义。此外，我们基于 5 个 PRGs 确定了两种不同的焦亡模式（焦亡聚类 A 和 B）。我们发现，聚类 B 中嗜酸粒细胞、γδT 细胞、巨噬细胞、自然杀伤细胞、调节性 T 细胞、辅助性 T 细胞 17 和辅助性 T 细胞 2 表达显著上调。并且，我们基于焦亡聚类 A 和 B 之间的 56 个差异表达基因（DEGs）确定了基因聚类 A 和 B。并计算了每个样本的焦亡评分以量化不同的模式。焦亡聚类 B 或基因聚类 B 中的患者的焦亡评分高于焦亡聚类 A 或基因聚类 A。
总之，PRGs 在 RA 的发生发展中起着重要作用。本研究结果可能为 RA 的免疫治疗策略提供新的思路。
