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. 2022 Jan 4:17:13-24.
doi: 10.2147/COPD.S333251. eCollection 2022.

Identification of the Key Immune-Related Genes in Chronic Obstructive Pulmonary Disease Based on Immune Infiltration Analysis

Affiliations

Identification of the Key Immune-Related Genes in Chronic Obstructive Pulmonary Disease Based on Immune Infiltration Analysis

Hongqiong Meng et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity worldwide. A better understanding of new biomarkers for COPD patients and their complex mechanisms in the progression of COPD are needed.

Methods: An algorithm was conducted to reveal the proportions of 22 subsets of immune cells in COPD samples. Differentially expressed immune-related genes (DE-IRGs) were obtained based on the differentially expressed genes (DEGs) of the GSE57148 dataset, and 1509 immune-related genes (IRGs) were downloaded from the ImmPort database. Functional enrichment analyses of DE-IRGs were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and Ingenuity Pathway Analysis (IPA). We defined the DE-IRGs that had correlations with immune cells as hub genes. The potential interactions among the hub genes were explored by a protein-protein interaction (PPI) network.

Results: The CIBERSORT results showed that lung tissue of COPD patients contained a greater number of resting NK cells, activated dendritic cells, and neutrophils than normal samples. However, the fractions of follicular helper T cells and resting dendritic cells were relatively lower. Thirty-eight DE-IRGs were obtained for further analysis. Functional enrichment analysis revealed that these DE-IRGs were significantly enriched in several immune-related biological processes and pathways. Notably, we also observed that DE-IRGs were associated with the coronavirus disease COVID-19 in the progression of COPD. After correlation analysis, six DE-IRGs associated with immune cells were considered hub genes, including AHNAK, SLIT2 TNFRRSF10C, CXCR1, CXCR2, and FCGR3B.

Conclusion: In the present study, we investigated immune-related genes as novel diagnostic biomarkers and explored the potential mechanism for COPD based on CIBERSORT analysis, providing a new understanding for COPD treatment.

Keywords: CIBERSORT; COPD; IRGs; chronic obstructive pulmonary disease; diagnosis; immune-related genes.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The profile of immune infiltration in COPD. (A) Immune infiltrating cell ratio between normal samples and COPD patients. (B) Comparison of the difference between immune infiltrating cells in COPD and normal samples. (C) Correlation of each immune infiltrating cell. The value represents the correlation coefficient between immune cells (range −1 to 1) were shown in the upper right half. Immune cells with higher, lower, and same correlation levels were shown in red, purple, and white, respectively. Significant P-values for correlations between immune cells were shown in the lower left half, * for P < 0.05, ** for P < 0.01, ***P < 0.0001.
Figure 2
Figure 2
Identification of differentially expressed immune-related genes. (A) Volcano map of differentially expressed genes. (B) Venn diagram of differentially expressed genes and immune-related genes. (C) Heat map of differentially expressed immune-related genes.
Figure 3
Figure 3
Functional enrichment analysis of differentially expressed immune-related genes. (A) Differential gene GO annotation visualization (Top 10) (bubble chart). (B) Differential gene KEGG annotation visualization (Top 10) (bubble chart). (C) Immune-related genes, differential gene enrichment, classical signaling pathways. (D) Immune-related differential gene enrichment of disease-related pathways.
Figure 4
Figure 4
Identification of hub genes in COPD. (A) Correlation diagram of differentially expressed genes and differential immune cells. (B) Scatter plot of immunological correlation between differentially expressed genes and differential immune cells. (C) PPI network of hub genes. (D) Boxplots showed the expression of hub genes between normal samples and COPD patients.
Figure 5
Figure 5
The diagnostic value of hub genes for COPD patients. (A) ROC curves of hub genes. (B) ROC curve of regression model based on hub genes.
Figure 6
Figure 6
The regulatory network of transcription factors and hub genes.

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