Wu Yi, Zhong Lin, Qiu Li, Dong Liqun, Yang Lin, Chen Lina
Division of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Front Genet. 2023 Jan 6;13:985217. doi: 10.3389/fgene.2022.985217. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease whose etiology remains unknown. This study aims to explore diagnostic biomarkers and pathways involved in IPF using bioinformatics analysis. IPF-related gene expression datasets were retrieved and downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, and weighted correlation network analysis (WGCNA) was performed to identify key module and genes. Functional enrichment analysis was performed on genes in the clinically significant module. Then least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were run to screen candidate biomarkers. The expression and diagnostic value of the biomarkers in IPF were further validated in external test datasets (GSE110147). 292 samples and 1,163 DEGs were screened to construct WGCNA. In WGCNA, the blue module was identified as the key module, and 59 genes in this module correlated highly with IPF. Functional enrichment analysis of blue module genes revealed the importance of extracellular matrix-associated pathways in IPF. IL13RA2, CDH3, and COMP were identified as diagnostic markers of IPF LASSO and SVM-RFE. These genes showed good diagnostic value for IPF and were significantly upregulated in IPF. This study indicates that IL13RA2, CDH3, and COMP could serve as diagnostic signature for IPF and might offer new insights in the underlying diagnosis of IPF.
特发性肺纤维化(IPF)是一种危及生命的疾病,其病因尚不清楚。本研究旨在利用生物信息学分析探索IPF相关的诊断生物标志物和通路。从NCBI基因表达综合数据库中检索并下载IPF相关基因表达数据集。筛选差异表达基因(DEG),并进行加权基因共表达网络分析(WGCNA)以识别关键模块和基因。对具有临床意义模块中的基因进行功能富集分析。然后运行最小绝对收缩和选择算子(LASSO)逻辑回归和支持向量机递归特征消除(SVM-RFE)算法来筛选候选生物标志物。在外部测试数据集(GSE110147)中进一步验证生物标志物在IPF中的表达和诊断价值。筛选出292个样本和1163个DEG用于构建WGCNA。在WGCNA中,蓝色模块被确定为关键模块,该模块中的59个基因与IPF高度相关。蓝色模块基因的功能富集分析揭示了细胞外基质相关通路在IPF中的重要性。通过LASSO和SVM-RFE确定IL13RA2、CDH3和COMP为IPF的诊断标志物。这些基因对IPF具有良好的诊断价值,且在IPF中显著上调。本研究表明,IL13RA2、CDH3和COMP可作为IPF的诊断标志物,可能为IPF的潜在诊断提供新的见解。