Abstract
Objectives Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation and remodeling. Macrophage polarization is associated with inflammation and tissue remodeling, as well as immunity. Therefore, this study attempts to investigate the diagnostic value and regulatory mechanism of macrophage polarization-related genes for COPD by bioinformatics analysis and to provide a new theoretical basis for experimental research. Methods The raw gene expression profile dataset (GSE124180) was collected from the Gene Expression Omnibus (GEO) database. Next, a weighted gene coexpression network analysis (WGCNA) was conducted to screen macrophage polarization-related genes. The differentially expressed genes (DEGs) between the COPD and normal samples were generated using DESeq2 v3.11 and overlapped with the macrophage polarization-related genes. Moreover, functional annotations of overlapped genes were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resource. The immune-related genes were selected, and their correlation with the differential immune cells was analyzed by Pearson. Finally, receiver operating characteristic (ROC) curves were used to verify the diagnostic value of genes. Results A total of 4922 coexpressed genes related to macrophage polarization were overlapped with the 203 DEGs between the COPD and normal samples, obtaining 25 genes related to COPD and macrophage polarization. GEM, S100B, and GZMA of them participated in the immune response, which were considered the candidate biomarkers. GEM and S100B were significantly correlated with marker genes of B cells which had a significant difference between the COPD and normal samples. Moreover, GEM was highly associated with the genes in the PI3K/Akt/GSK3β signaling pathway, regulation of actin cytoskeleton, and calcium signaling pathway based on a Pearson correlation analysis of the candidate genes and the genes in the B cell receptor signaling pathway. PPI network analysis also indicated that GEM might participate in the regulation of the PI3K/Akt/GSK3β signaling pathway. The ROC curve showed that GEM possessed an excellent accuracy in distinguishing COPD from normal samples. Conclusions The data provide a transcriptome-based evidence that GEM is related to COPD and macrophage polarization likely contributes to COPD diagnosis. At the same time, it is hoped that in-depth functional mining can provide new ideas for exploring the COPD pathogenesis.
Highlights
Chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung mainly caused by smoking tobacco cigarettes and environmental exposure from burning biomass fuels or air pollution [1, 2], has become a major health problem around the world [3]
The analysis of the relationship of the modules and the traits suggested that multiple modules were closely related to one or more traits, especially the black module, which was the one with the highest correlation coefficient strongly associated with the macrophage polarization (Figure 1(c))
Baschal et al compared the gene expressions across the lower airway, sinus, and middle ear tissues using the GSE124180 dataset and other data [43]. Different from these two researches, our study mainly focused on the role of macrophage polarization in COPD and identification of macrophage polarization-related genes as the biomarkers of COPD based on the peripheral blood of the GSE124180 dataset
Summary
Chronic obstructive pulmonary disease (COPD), an inflammatory disease of the lung mainly caused by smoking tobacco cigarettes and environmental exposure from burning biomass fuels or air pollution [1, 2], has become a major health problem around the world [3]. It has been reported that COPD killed about 3 million people in 2016, and the mortality rates of COPD are still growing [4]. Even if some pulmonary rehabilitation programs, such as exercise training, education, and behavior change followed by patient-tailored therapies have been regarded as promising measures for improving the COPD patients, a few patients still cannot gain the benefit from the exercise training [10].
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