Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease with multiple system involvement, and pulmonary complications, including pulmonary hypertension (PH), are leading causes of death. This study aimed to develop early biomarkers to distinguish SSc with or without PH from normal population using bioinformatics approaches. The gene expression profile GSE22356, which contains 10 SSc samples with PH, 10 SSc samples without PH, and 10 normal samples, was obtained from the Gene Expression Omnibus database. First, we constructed co-expression networks and identified critical gene modules using the weighted gene co-expression network analysis. Then, functional enrichment analysis of significant modules was performed. Finally, the “real” hub gene was screened out by intramodule analysis and protein–protein interaction networks, and the receiver operating characteristic analysis was conducted. A total of 5046 genes were screened out to construct co-expression networks, and 18 modules were identified. Of these modules, the turquoise module had a strong correlation with SSc only, whereas the midnightblue module showed an obvious positive correlation with SSc with PH. Functional enrichment analysis indicated that the turquoise module was mainly enriched in transcription of DNA template and its regulation and protein ubiquitination and involved in apoptosis and pyrimidine metabolism pathway. The midnightblue module was significantly associated with inflammatory and immune response and pathways in Staphylococcus aureus infection and Chagas disease. The “real” hub genes in the turquoise module were WDR36, POLR1B, and SRSF1, and those in midnightblue were TLR2 and TNFAIP6.

中文翻译：

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使用共表达分析鉴定与伴或不伴肺动脉高压的系统性硬化症相关的生物标志物

系统性硬化症 (SSc)，也称为硬皮病，是一种多系统受累的自身免疫性疾病，包括肺动脉高压 (PH) 在内的肺部并发症是导致死亡的主要原因。本研究旨在开发早期生物标志物，以使用生物信息学方法将有或没有 PH 的 SSc 与正常人群区分开来。基因表达谱 GSE22356 包含 10 个有 PH 的 SSc 样本、10 个没有 PH 的 SSc 样本和 10 个正常样本，是从 Gene Expression Omnibus 数据库中获得的。首先，我们构建了共表达网络并使用加权基因共表达网络分析确定了关键基因模块。然后，对重要模块进行功能富集分析。最后，通过模块内分析和蛋白质-蛋白质相互作用网络筛选出“真正的”枢纽基因，并进行了受试者工作特征分析。共筛选出5046个基因构建共表达网络，鉴定出18个模块。在这些模块中，绿松石模块仅与 SSc 具有强相关性，而午夜蓝模块与 SSc 与 PH 显示出明显的正相关。功能富集分析表明，绿松石模块主要富集于DNA模板的转录及其调控和蛋白泛素化，并参与细胞凋亡和嘧啶代谢途径。午夜蓝模块与炎症和免疫反应以及通路显着相关 在这些模块中，绿松石模块仅与 SSc 具有强相关性，而午夜蓝模块与 SSc 与 PH 显示出明显的正相关。功能富集分析表明，绿松石模块主要富集于DNA模板的转录及其调控和蛋白泛素化，并参与细胞凋亡和嘧啶代谢途径。午夜蓝模块与炎症和免疫反应以及通路显着相关 在这些模块中，绿松石模块仅与 SSc 具有强相关性，而午夜蓝模块与 SSc 与 PH 显示出明显的正相关。功能富集分析表明，绿松石模块主要富集于DNA模板的转录及其调控和蛋白泛素化，并参与细胞凋亡和嘧啶代谢途径。午夜蓝模块与炎症和免疫反应以及通路显着相关 功能富集分析表明，绿松石模块主要富集于DNA模板的转录及其调控和蛋白质泛素化，并参与细胞凋亡和嘧啶代谢途径。午夜蓝模块与炎症和免疫反应以及通路显着相关 功能富集分析表明，绿松石模块主要富集于DNA模板的转录及其调控和蛋白泛素化，并参与细胞凋亡和嘧啶代谢途径。午夜蓝模块与炎症和免疫反应以及通路显着相关金黄色葡萄球菌感染和恰加斯病。绿松石模块中的“真正”中枢基因是WDR36、POLR1B和SRSF1，而午夜蓝中的那些是TLR2和TNFAIP6。