Pan Yanqing, Shi Binbing, Zang Fangnan, Ji Yi, Zhang Xiuli, Zhang Changxi, Sun Qi, Li Chenyang, Zhu Hong, Pan Defeng
Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, 221004, Jiangsu, China.
Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Clin Rheumatol. 2025 Jun 20. doi: 10.1007/s10067-025-07479-9.
Clinical and epidemiological studies suggest a notably higher incidence of atherosclerosis (AS) in systemic sclerosis (SSc) patients, yet their shared molecular mechanisms remain unclear. Therefore, this research was designed to investigate the shared pathogenic mechanisms underlying both SSc and AS.
SSc and AS datasets were acquired from the Gene Expression Omnibus (GEO) database to identify common differentially expressed genes (DEGs). Subsequently, enrichment analyses, protein-protein interaction (PPI) network analysis, coexpression analysis, and TF-mRNA-miRNA regulatory network construction were performed on these common DEGs. Finally, the hub genes were validated using external datasets. Additionally, immune cell infiltration in both SSc and AS was analyzed via the CIBERSORT algorithm, and the relationships between hub genes and immune cell infiltration were assessed.
A total of 104 DEGs were identified, with 99 upregulated and 5 downregulated genes. Functional enrichment analysis indicated that the pathogenic mechanisms of these genes are related to immune processes. Through comprehensive bioinformatics analysis, three hub genes (ITGB2, CD163, and CCR5) were identified. Comparative analysis revealed marked upregulation of these genes in pathological specimens relative to controls, highlighting their diagnostic biomarker potential. Furthermore, immune profiling demonstrated macrophage and T lymphocyte predominance in disease microenvironments, implicating these immune populations in SSc and AS pathogenesis.
Our study revealed common biomarkers and immune-related pathways that may contribute to the pathogenesis of both SSc and AS. These findings suggest potential immunological mechanisms underlying the development of AS in patients with SSc, providing new insights into the pathological links between these two diseases. Key Points • ITGB2, CD163, and CCR5 may be new diagnostic biomarkers for SSc and AS. • Macrophages and T lymphocytes as key mediators in SSc and AS pathogenesis.
临床和流行病学研究表明，系统性硬化症（SSc）患者动脉粥样硬化（AS）的发病率显著更高，但其共同的分子机制仍不清楚。因此，本研究旨在探讨SSc和AS共同的致病机制。
从基因表达综合数据库（GEO）获取SSc和AS数据集，以识别共同的差异表达基因（DEG）。随后，对这些共同的DEG进行富集分析、蛋白质-蛋白质相互作用（PPI）网络分析、共表达分析和转录因子-信使核糖核酸-微小核糖核酸调控网络构建。最后，使用外部数据集验证枢纽基因。此外，通过CIBERSORT算法分析SSc和AS中的免疫细胞浸润情况，并评估枢纽基因与免疫细胞浸润之间的关系。
共鉴定出104个DEG，其中99个基因上调，5个基因下调。功能富集分析表明，这些基因的致病机制与免疫过程有关。通过综合生物信息学分析，确定了三个枢纽基因（整合素β2（ITGB2）、CD163和C趋化因子受体5（CCR5））。比较分析显示，相对于对照，这些基因在病理标本中显著上调，突出了它们作为诊断生物标志物的潜力。此外，免疫谱分析表明，疾病微环境中巨噬细胞和T淋巴细胞占主导地位，提示这些免疫细胞群体参与了SSc和AS的发病机制。
我们的研究揭示了可能导致SSc和AS发病的共同生物标志物和免疫相关途径。这些发现提示了SSc患者AS发生发展潜在的免疫机制，为这两种疾病之间的病理联系提供了新的见解。要点：• ITGB2、CD163和CCR5可能是SSc和AS的新诊断生物标志物。• 巨噬细胞和T淋巴细胞是SSc和AS发病机制中的关键介质。
