Division of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, People's Republic of China.
BMC Med Genomics. 2022 May 12;15(1):110. doi: 10.1186/s12920-022-01241-9.
Asthma is a chronic lung disease characterized by reversible inflammation of the airways. The imbalance of Th1/Th2 cells plays a significant role in the mechanisms of asthma. The aim of this study was to identify asthma-related key genes and functionally enriched pathways in a Th2-high group by using weighted gene coexpression network analysis (WGCNA).
The gene expression profiles of GSE4302, which included 42 asthma patients and 28 controls, were selected from the Gene Expression Omnibus (GEO). A gene network was constructed, and genes were classified into different modules using WGCNA. Gene ontology (GO) was performed to further explore the potential function of the genes in the most related module. In addition, the expression profile and diagnostic capacity (ROC curve) of hub genes of interest were verified by dataset GSE67472.
In dataset GSE4302, subjects with asthma were divided into Th2-high and Th2-low groups according to the expression of the SERPINB2, POSTN and CLCA1 genes. A weighted gene coexpression network was constructed, and genes were classified into 7 modules. Among them, the red module was most closely associated with Th2-high asthma, which contained 60 genes. These genes were significantly enriched in different biological processes and molecular functions. A total of 8 hub genes (TPSB2, CPA3, ITLN1, CST1, SERPINB10, CEACAM5, CHD26 and P2RY14) were identified, and the expression levels of these genes (except TPSB2) were confirmed in dataset GSE67472. ROC curve analysis validated that the expression of these 8 genes exhibited excellent diagnostic efficiency for Th2-high asthma and Th2-low asthma.
The study provides a novel perspective on Th2-high asthma by WGCNA, and the hub genes and potential pathways involved may be beneficial for the diagnosis and management of Th2-high asthma.
哮喘是一种以气道可逆性炎症为特征的慢性肺部疾病。Th1/Th2 细胞失衡在哮喘发病机制中起着重要作用。本研究旨在通过加权基因共表达网络分析（WGCNA）鉴定 Th2 高组中与哮喘相关的关键基因和功能富集途径。
从基因表达综合数据库（GEO）中选择基因表达谱数据集 GSE4302，该数据集包括 42 例哮喘患者和 28 例对照。构建基因网络，使用 WGCNA 将基因分类为不同的模块。进行基因本体论（GO）分析，以进一步探索最相关模块中基因的潜在功能。此外，通过数据集 GSE67472 验证感兴趣的枢纽基因的表达谱和诊断能力（ROC 曲线）。
在数据集 GSE4302 中，根据 SERPINB2、POSTN 和 CLCA1 基因的表达，将哮喘患者分为 Th2 高和 Th2 低两组。构建了加权基因共表达网络，并将基因分类为 7 个模块。其中，红色模块与 Th2 高哮喘最为密切相关，包含 60 个基因。这些基因在不同的生物学过程和分子功能中显著富集。共鉴定出 8 个枢纽基因（TPSB2、CPA3、ITLN1、CST1、SERPINB10、CEACAM5、CHD26 和 P2RY14），并在数据集 GSE67472 中证实了这些基因的表达水平（除 TPSB2 外）。ROC 曲线分析验证了这些 8 个基因的表达对 Th2 高哮喘和 Th2 低哮喘具有优异的诊断效率。
本研究通过 WGCNA 为 Th2 高哮喘提供了新的视角，所涉及的枢纽基因和潜在途径可能有助于 Th2 高哮喘的诊断和管理。
