Abstract
BACKGROUND AND AIMS: Alveolar macrophages (AM) play a crucial role in the development of chronic obstructive pulmonary disease (COPD). The role that AM plays in the molecular pathways and clinical phenotypes associated with tobacco-related emphysema remain poorly understood. Thus, we investigated the transcriptomic profile of AM in COPD patients with a history of smoking and explored the molecular mechanisms associated with enriched pathways and hub genes. METHODS: Four data sets (GSE2125, GSE8823, GSE13896 and GSE130928) were retrieved from the GEO Database. A total of 203 GEO samples (GSM) were collated for this study. About 125 of these cases were classified as smokers (91 as healthy non-COPD smokers and 34 as COPD smokers). Based on the bioinformatics obtained using the R3.6.1 program, the data were successively adopted for differential genetic expression analysis, enrichment analysis (EA), and then protein-protein interaction analysis (PPI) in a STRING database. Finally, Cytoscape 3.8 software was used to screen the hub genes. A further data analysis was performed using a set of 154 cases, classified as 64 healthy non-smokers and 91 as healthy smokers. The same procedures were used as for the COPD dataset. RESULTS: When comparing the data pertaining to COPD-smokers and non-COPD smokers, the top ten genes with the greatest transcriptional differences were found to be NADK, DRAP1, DEDD, NONO, KLHL12, PRKAR1A, ITGAL, GLE1, SLC8A1, SVIL. A GSEA (Gene Set Enrichment Analysis) revealed that these genes manifested an up-regulated ribosomal pathway in contrast with other genes that exhibited an extensive down-regulated pathway. The hub genes were mainly genes encoding ribosomal subunits through PPI. Furthermore, it was found that there is a narrow transcriptional difference between healthy non-smokers and non-COPD smokers and the hub genes identified here are mainly members of the chemokines, including CCL5, CCR5, CXCL9 and CXCL11. CONCLUSION: An elevated activity of the ribosome pathway in addition to the increased expression of ribosomal housekeeping genes (also known as hub genes) were identified with COPD-smokers, and these have the potential to cause a wide range of downstream pathogenetic effects. As for the preclinical phase, non-COPD smokers were found to be characterized by enriched pathways of several chemokines in AM.