Zhao Pei, Yuan Kexin, Tang Zhipeng, Li Yonghui, Yu Yueqing, Gao Wei, Zhang Yu, Wang Jie, Li Xinxin, Tie Yanqing
Hebei Key Laboratory of Molecular Medicine, Shijiazhuang, 050051, China.
Hebei Clinical Research Center for Laboratory Medicine, Shijiazhuang, 050051, China.
Clin Rheumatol. 2025 Apr 28. doi: 10.1007/s10067-025-07423-x.
Study found that patients with rheumatoid arthritis (RA) are more likely to develop atherosclerosis than normal adults. However, their shared mechanisms of action still remain unclear. This study aimed to identify the shared genes between the two diseases and uncover their regulatory mechanisms.
The RA- and atherosclerosis-related microarray datasets were downloaded from public databases. Gene set enrichment, differential expression, and weighted gene co-expression network analyses were performed to identify the shared genes between the two diseases. Functional enrichment analysis and protein-protein interaction networks for shared genes were performed. Through further expression validation using validation datasets, hub-shared genes were identified. The diagnostic values of hub-shared genes and their related transcription factors (TFs), small-molecule drugs, and immune cells were analyzed.
A total of 82 shared genes, which were significantly involved in nine pathways, including the peroxisome proliferator-activated receptor signaling pathway and Th1 and Th2 cell differentiation, were identified. Two hub-shared genes, CD52 and TNFRSF17, were screened out using validation. CD52 and TNFRSF17 showed high diagnostic performance for both diseases. CD52 and TNFRSF17 could interact with multiple proteins, including TNFSF13, and are regulated by several TFs, including NFKB1 and MEF2A. Moreover, significant correlations were observed between hub-shared genes and the infiltration of several immune cells in the two diseases, such as between gamma delta T cells and TNFRSF17, as well as between neutrophils and CD52.
Two hub-shared genes, CD52 and TNFRSF17, may be key regulators in the development of RA and atherosclerosis. Key Points • Study found that patients with RA are more likely to develop atherosclerosis. The shared mechanisms of action between the two diseases are unclear. We used bioinformatics methods to investigate shared genes and explore the mechanisms. • Our results indicated that the two hub genes, CD52 and TNFRSF17, may be key regulators in the development of atherosclerosis in RA. Further research of these two genes may reveal the mechanism that RA patients are more likely to suffer from atherosclerosis.
研究发现类风湿关节炎（RA）患者比正常成年人更易患动脉粥样硬化。然而，它们共同的作用机制仍不清楚。本研究旨在确定这两种疾病之间的共同基因，并揭示其调控机制。
从公共数据库下载与RA和动脉粥样硬化相关的微阵列数据集。进行基因集富集、差异表达和加权基因共表达网络分析，以确定两种疾病之间的共同基因。对共同基因进行功能富集分析和蛋白质-蛋白质相互作用网络分析。通过使用验证数据集进行进一步的表达验证，确定枢纽共同基因。分析枢纽共同基因及其相关转录因子（TFs）、小分子药物和免疫细胞的诊断价值。
共鉴定出82个共同基因，这些基因显著参与9条信号通路，包括过氧化物酶体增殖物激活受体信号通路以及Th1和Th2细胞分化。通过验证筛选出两个枢纽共同基因CD52和TNFRSF17。CD52和TNFRSF17对两种疾病均表现出较高的诊断效能。CD52和TNFRSF17可与多种蛋白质相互作用，包括TNFSF13，并受多种TFs调控，包括NFKB1和MEF2A。此外，在两种疾病中观察到枢纽共同基因与几种免疫细胞的浸润之间存在显著相关性，如γδT细胞与TNFRSF17之间以及中性粒细胞与CD52之间。
两个枢纽共同基因CD52和TNFRSF17可能是RA和动脉粥样硬化发生发展的关键调节因子。要点 • 研究发现RA患者更易患动脉粥样硬化。两种疾病之间共同的作用机制尚不清楚。我们使用生物信息学方法研究共同基因并探索其机制。 • 我们的结果表明，两个枢纽基因CD52和TNFRSF17可能是RA患者动脉粥样硬化发生发展的关键调节因子。对这两个基因的进一步研究可能揭示RA患者更易患动脉粥样硬化的机制。
