Identification of Hub Genes Associated with COPD Through Integrated Bioinformatics Analysis

International Journal of COPD

关键词: copd;    geo;    wgcna;    cigarette;    bioinformatics.;   

DOI  :  

来源: DOAJ

【 摘 要 】

Lin Chen,1,2 Donglan Zhu,1 Jinfu Huang,1 Hui Zhang,1 Guang Zhou,1 Xiaoning Zhong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Liuzhou People’s Hospital, LiuZhou, Guangxi, People’s Republic of ChinaCorrespondence: Xiaoning Zhong, Tel [phone], Fax [phone], Email [e-mail]: Smoking is recognized as a risk factor for Chronic Obstructive Pulmonary Disease (COPD), yet only 20– 25% of smokers eventually develop COPD. Since its molecular pathogenesis remains unclear, there is an important need to further understand genetic differences between smokers with COPD and healthy smokers, screen out high-risk and susceptible groups among smokers, and find effective therapeutic targets.Methods: Bioinformatics tools were used to screen biomarkers that were significantly associated with COPD smokers and healthy smokers. qRT-PCR and Western blotting analysis were used to detect hub gene expression in CSE-treated BEAS-2B cells and lung tissue of COPD mouse models.Results: Our study identified 132 DEGs. The GO and KEGG analyses suggested that the ECM-receptor interaction, MAPK signaling pathway, Chemokine signaling pathway, PI3K-Akt signaling pathway, extracellular matrix organization and collagen fibril organization were associated with the occurrence and development of COPD. In addition, WGCNA analysis of GSE1650 showed that the brown module was most correlated with COPD. The intersection between the brown module and DEGs was used to identify 9 HUB genes (COL14A1, SULF1, MOXD1, CXCL12, CHRNA1, COMP, POU2AF1, MMP11, THBS2) that showed consistent expression and upregulation. Both the mRNA and protein expression levels of the Hub genes (except that of MMP11) were significantly upregulated in tobacco smoke exposed mouse emphysema models and CSE treated BEAS-2B cells.Conclusion: Our results suggest that COL14A1, SULF1, MOXD1, CXCL12, CHRNA1, COMP, POU2AF1, and THBS2 may be potentially useful biomarkers for identifying smokers with a risk of developing COPD. The GO and KEGG functional enrichment analyses further confirmed the significant role played by ECM in the pathogenesis of COPD. The results of this study may provide further insights into the pathogenetic mechanisms involved in COPD.Keywords: COPD, GEO, WGCNA, cigarette, bioinformatics

【 授权许可】

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