BackgroundEvidence is accumulating to characterise the key differences between systemic sclerosis (SSc) and rheumatoid arthritis (RA), which are similar but distinct systemic autoimmune diseases. However, the differences at the genetic level are not yet clear. Therefore, the aim of the present study was to identify key differential genes between patients with SSc and RA.MethodsThe Gene Expression Omnibus database was used to identify differentially expressed genes (DEGs) between SSc and RA biopsies. The DEGs were then functionally annotated using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. A protein–protein interaction (PPI) network was constructed with Cytoscape software. The Molecular Complex Detection (MCODE) plugin was also used to evaluate the biological importance of the constructed gene modules.ResultsA total of 13,556 DEGs were identified between the five SSc patients and seven RA patients, including 13,465 up-regulated genes and 91 down-regulated genes. Interestingly, the most significantly enriched GO terms of up- and down-regulated genes were related to extracellular involvement and immune activity, respectively, and the top six highly enriched KEGG pathways were related to the same processes. In the PPI network, the top 10 hub nodes and top four modules harboured the most relevant genes contributing to the differences between SSc and RA, including key genes such as IL6, EGF, JUN, FGF2, BMP2, FOS, BMP4, LRRK2, CTNNB1, EP300, CD79, and CXCL13.ConclusionsThese genes such as IL6, EGF, JUN, FGF2, BMP2, FOS, BMP4, LRRK2, CTNNB1, EP300, CD79, and CXCL13 can serve as new targets for focused research on the distinct molecular pathogenesis of SSc and RA. Furthermore, these genes could serve as potential biomarkers for differential diagnoses or therapeutic targets for treatment.

中文翻译：

---

系统性硬化症和类风湿性关节炎的差异表达基因

背景越来越多的证据表明系统性硬化症 (SSc) 和类风湿性关节炎 (RA) 之间的主要区别是相似但不同的系统性自身免疫性疾病。然而，基因水平的差异尚不清楚。因此，本研究的目的是鉴定SSc和RA患者之间的关键差异基因。方法基因表达综合数据库用于鉴定SSc和RA活检之间的差异表达基因（DEGs）。然后使用基因本体论 (GO) 术语和京都基因和基因组百科全书 (KEGG) 途径以及注释、可视化和集成发现 (DAVID) 工具对 DEG 进行功能注释。使用 Cytoscape 软件构建了蛋白质-蛋白质相互作用 (PPI) 网络。分子复合物检测（MCODE）插件还用于评估构建的基因模块的生物学重要性。结果在5名SSc患者和7名RA患者之间共鉴定出13556个DEGs，其中13465个上调基因和91个下调基因基因。有趣的是，上调和下调基因中最显着富集的 GO 术语分别与细胞外参与和免疫活性有关，而前 6 个高度富集的 KEGG 途径与相同的过程有关。在 PPI 网络中，前 10 个 hub 节点和前 4 个模块包含了导致 SSc 和 RA 差异的最相关基因，包括 IL6、EGF、JUN、FGF2、BMP2、FOS、BMP4、LRRK2、CTNNB1 等关键基因, EP300, CD79, 和 CXCL13. 结论这些基因如 IL6, EGF, JUN, FGF2, BMP2, FOS, BMP4、LRRK2、CTNNB1、EP300、CD79 和 CXCL13 可以作为重点研究 SSc 和 RA 不同分子发病机制的新靶点。此外，这些基因可以作为鉴别诊断的潜在生物标志物或治疗的治疗靶点。