Dataset Information

Bioinformatics analyses of the pathogenesis and new biomarkers of chronic obstructive pulmonary disease

ABSTRACT: Abstract

Background:

Chronic obstructive pulmonary disease (COPD) is one of the major cause of global death. The purpose of our analysis was to detect a more reliable biomarker and small-molecule drug candidates and to identify the precise mechanisms involved in COPD.

Methods:

Three data sets were downloaded from the Gene Expression Omnibus database and analysed by Gene Expression Omnibus 2R. Functional enrichment analyses were performed by Metascape. We use the STRING data to build a protein–protein interaction network. The targets of differentially expressed microRNA (DE miRNA) were predicted by the miRWalk database. Small-molecule drugs were predicted on connectivity map.

Results:

A total of 181 differentially expressed genes and 35 DE miRNAs were confirmed. The protein–protein interaction network including all integrated differentially expressed genes was constructed, and 4 modules were filtrated. The module genes were relative to immune, inflammatory and oxidative stress functions according to a pathway analysis. The top 20 key genes were screened. Among the DE miRNAs found to be regulating key genes, miR-194-3p, MiR-502-5p, MiR-5088-5p, MiR-3127-5p, and miR-23a-5p might be the most significant due to their high number of connecting nodes in COPD. In addition, cephaeline, emetine, gabapentin, and amrinone were found to be potential drugs to treat COPD patients.

Conclusion:

Our study suggests that miR-194-3p, miR-502-5p, and miR-23a-5p might participate in the nosogenesis of COPD. In addition, 4 potential small-molecule drugs were considered potentially useful for treating COPD patients.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8601278 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesChronic 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.MethodsThe 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.ResultsA 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.ConclusionsThe 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.