Key Immune-Related Genes in Chronic Obstructive Pulmonary Disease

Six genes expressing correlations with immune cells have been identified that may have a significant influence on chronic obstructive pulmonary disease (COPD): AHNAK, SLIT2, TNFRRSF10C, CXCR1, CXCR2, and FCGR3B. Further study of these genes, which may serve as control targets for COPD, could lead to new therapies, according to research findings published in the International Journal of Chronic Obstructive Pulmonary Disease.

Researchers in China used an algorithm 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 of the GSE57148 dataset. “Hub genes” were defined as the DE-IRGs that expressed correlations with immune cells. Potential interactions among hub genes were explored via a protein-protein interaction network.

Matrix files of the GSE57148 dataset based on the GPL11154 platform were extracted from the Gene Expression Omnibus database, which contained 98 COPD and 91 normal individuals. Researchers also downloaded the GSE76925 dataset, which contains RNA sequencing data from 111 COPD cases and 40 normal lung tissues, for diagnostic marker expression assessment and validation of diagnostic value. Additionally, 1509 IRGs were obtained from the ImmPort database.

Using the CIBERSORT algorithm to analyze differences between COPD and normal samples, the investigators found that lung tissue of COPD patients contained a greater number of resting natural killer (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.

Further analysis was performed on 38 DE-IRGs. Functional enrichment analysis revealed that these DE-IRGs were significantly enriched in several immune-related biological processes and pathways. The researchers also noted that these DE-IRGs were associated with COVID-19 in the progression of COPD. Correlation analysis indicated 6 DE-IRGs associated with immune cells that were considered hub genes: AHNAK, SLIT2, TNFRRSF10C, CXCR1, CXCR2, and FCGR3B.

“This study found differential immune cells in COPD samples, which can provide new ideas for the treatment of COPD,” said the investigators, adding that novel diagnostic biomarkers are essential for predicting the severity of COPD or the possibility of developing the disease among people exposed to risk factors. They added that, “Based on the theory of the immune mechanism of COPD in recent years, a variety of new immunomodulatory drugs can promote damaged airway repair or reconstruction of immunity, thereby reducing the frequency and severity of COPD attacks and improving health status and exercise tolerance.”

Reference

Meng H, Long Q, Wang R, et al. Identification of the key immune-related genes in chronic obstructive pulmonary disease based on immune infiltration analysis. Int J Chron Obstruct Pulmon Dis. Published online January 4, 2022. doi.org/10.2147/COPD.S333251