Objective 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. Method 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. Results 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. Conclusion Two hub-shared genes, CD52 and TNFRSF17, may be key regulators in the development of RA and atherosclerosis. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> 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. </entry> </row> </tbody> </tgroup> </Table>

Investigation of hub-shared genes and regulatory mechanisms of rheumatoid arthritis and atherosclerosis

期刊论文
发表日期：

2025年4月28日

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Pei Zhao,
Kexin Yuan,
Zhipeng Tang,
Yonghui Li,
Yueqing Yu,
Wei Gao,
Yu Zhang,
Jie Wang,
Xinxin Li,
Yanqing Tie

摘要

Objective

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.

Method

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.

Results

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.

Conclusion

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.