Background. Pulmonary complications of systemic sclerosis (SSc), including pulmonary arterial hypertension (PAH), are the leading causes of patient death. However, the precise molecular mechanisms of its etiology are unclear. This study’s objective was to identify the candidate genes involved in the progression of SSc-PAH and investigate the genes' function. Methods. The gene expression profiles of GSE33463 were obtained from the Gene Expression Omnibus (GEO) database. A free-scale gene coexpression network was constructed using the weighted gene coexpression network analysis (WGCNA) to explore the association between gene sets and clinical features and identify candidate biomarkers. Then, gene ontology analysis was performed. A second dataset was used, GSE19617, to validate the hub genes. The verified hub genes’ potential function was further explored using gene set enrichment analysis (GSEA). Results. Through average link-level clustering, a total of seven modules were classified. A total of 938 hub genes were identified in the key module, and the key module’s function mainly enriched was related to chemokine activities. Subsequently, four candidate genes, BTG3, CCR2, RAB10, and TMEM60, were filtered. The expression levels of these four hub genes were consistent in the GSE19617 and GSE33463 datasets. We plotted the ROC curve of the hub genes (all ). Furthermore, the results of the GSEA for hub genes were correlated with complement and inflammatory responses. Conclusions. The hub genes (BTG3, CCR2, RAB10, and TMEM60) performed well in distinguishing the SSc-PAH patients from controls, and some biological functions, related to immunity, inflammation, and cytokines, might pave the way for follow-up studies on the diagnosis and treatment of SSc-PAH.

中文翻译：

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在系统性硬化症相关肺动脉高压中鉴定的候选基因与免疫、炎症和细胞因子有关

背景。系统性硬化症 (SSc) 的肺部并发症，包括肺动脉高压 (PAH)，是导致患者死亡的主要原因。然而，其病因的确切分子机制尚不清楚。本研究的目的是确定参与 SSc-PAH 进展的候选基因并研究这些基因的功能。方法. GSE33463 的基因表达谱来自基因表达综合 (GEO) 数据库。使用加权基因共表达网络分析（WGCNA）构建了一个自由尺度的基因共表达网络，以探索基因集与临床特征之间的关联并确定候选生物标志物。然后，进行基因本体分析。使用第二个数据集 GSE19617 来验证中心基因。使用基因集富集分析（GSEA）进一步探索验证的枢纽基因的潜在功能。结果. 通过平均链路级聚类，共分类了七个模块。关键模块共鉴定出938个中枢基因，关键模块主要富集的功能与趋化因子活性有关。随后，筛选了四个候选基因，BTG3、CCR2、RAB10 和 TMEM60。这四个中心基因的表达水平在 GSE19617 和 GSE33463 数据集中是一致的。我们绘制了中心基因的 ROC 曲线（所有）。此外，中枢基因的 GSEA 结果与补体和炎症反应相关。结论。枢纽基因（BTG3、CCR2、RAB10 和 TMEM60）在区分 SSc-PAH 患者和对照组方面表现良好，一些与免疫、炎症和细胞因子相关的生物学功能可能为后续研究铺平道路。 SSc-PAH的诊断和治疗。