Abstract
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 AUC > 0.70). 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.
Highlights
Systemic sclerosis (SSc), with a chronic progressive manner, is a rare systemic autoimmune disease [1]
Lung involvement in systemic sclerosis (SSc) consists of both interstitial lung diseases (ILD) and pulmonary hypertension (PAH), and it is worth noting that pulmonary arterial hypertension (PAH) is not uncommon in SSc [3] and might be more common in limited SSc [4]
The exercise capacity and quality of life have significantly improved in patients with idiopathic PAH (IPAH) due to vasodilators uses, there is no such trend in patients with SSc-related PAH (SSc-PAH) [2]
Summary
Systemic sclerosis (SSc), with a chronic progressive manner, is a rare systemic autoimmune disease [1]. Lung involvement is a common cause of mortality in patients with SSc [8], of which ILD is the most common, followed by PAH [6]. Pulmonary complications of systemic sclerosis (SSc), including pulmonary arterial hypertension (PAH), are the leading causes of patient death. This study’s objective was to identify the candidate genes involved in the progression of SSc-PAH and investigate the genes' function. 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. 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
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