Dataset Information

Identification of Macrophage Polarization-Related Genes as Biomarkers of Chronic Obstructive Pulmonary Disease Based on Bioinformatics Analyses.

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.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC8238569 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeFerroptosis and immune infiltration are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We aim to identify ferroptosis-related hub genes and analyze their association with immune infiltration in COPD through bioinformatics methods.Materials and methodsThe mRNA microarray data of GSE38974 were downloaded from Gene Expression Omnibus to obtain differentially expressed genes (DEGs). The DEGs were intersected with ferroptosis-related genes (FRGs) from FerrDb to obtain differentially expressed FRGs. GO and KEGG enrichment and protein-protein interaction (PPI) analyses of differentially expressed FRGs were conducted in R software and STRING database. The key module and hub genes were screened by Cytoscape software. MiRNAs, transcription factors and signal molecules were predicted in miRNet and NetworkAnalyst. The disease correlation in the Comparative Toxicomics Database (CTD) and the receiver operating characteristic (ROC) curves of hub genes were analyzed. Immune infiltration was evaluated by CIBERSORT algorithm. Spearman correlation analyses were conducted between hub genes and differentially infiltrated immune cells.ResultsFifteen differentially expressed FRGs were identified, which were enriched in some terms involving airway inflammatory responses and structural remodeling. Five hub genes were selected including HIF1A, IL6, PTGS2, CDKN1A and ATM. Inference scores in CTD indicated their association with COPD. Two miRNAs, five transcription factors and one signal molecule were predicted. The combination of hub genes could be a fine diagnostic indicator of COPD (AUC: 0.981, CI: 0.940-1.000). Immune infiltration evaluation showed that monocytes and M0 macrophages were upregulated in COPD lung tissues, while CD8 T cells, activated NK cells, M2 macrophages, resting dendritic cells and resting mast cells were downregulated. The hub genes were significantly associated with differentially infiltrated immune cells.ConclusionWe identified five ferroptosis-related hub genes (HIF1A, IL6, PTGS2, CDKN1A and ATM) in COPD, and found that they may influence the pathogenesis of COPD by regulating ferroptosis and thus affecting infiltrating immune cells.

Project description:PurposeAs a common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality. Current clinical therapies are not ideal and do not improve lung function or long-term life quality. It is very important to find new potential pathogenic mechanisms, biomarkers, and targets with therapeutic value in COPD.MethodsSerum samples collected from acute exacerbation and stable COPD and healthy participants were analyzed using label-free liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins (DEPs) between two groups. Bioinformatics analyses were performed to determine the biological processes associated with those DEPs. Key proteins were validated by enzyme linked immunosorbent assay (ELISA).ResultsIn total, 661 proteins were detected in serum from patients with COPD and healthy participants. Compared with healthy participants, patients with acute exacerbation of COPD had 45 DEPs, 13 were upregulated and 32 were downregulated; and patients with stable COPD had 79 DEPs, 18 were upregulated and 61 were downregulated. Gene Ontology functional annotation results indicated that the DEPs identified in patients with COPD were associated with the terms cellular anatomical entity, binding, and cellular process. Kyoto Encyclopedia of Genes and Genomes functional annotation analysis and the Clusters of Orthologous Genes database analysis indicated that the functions of these DEPs were primarily in signal transduction mechanisms and amino acid transport and metabolism. The ELISA results for three key proteins of IGFBP2, LRG1 and TAGLN were consistent with the LC-MS/MS results and the area under the receiver operating characteristic of the combined index was 0.893 (95% CI: 0.813, 0.974).ConclusionOur findings suggested pathogenic mechanisms underlying COPD stages and indicated three key proteins that may warrant further study as potential biomarkers for early diagnosis or prognosis of COPD or as therapeutic targets.