Integrative bioinformatics analyses reveal new molecular signatures and immune infiltration in chronic obstructive pulmonary disease: mediators of airflow limitation

Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive airflow limitation and lacks clear molecular pathogenesis. We aimed to screen potential key genes and immune infiltration traits in COPD progression by bioinformatics analyses. Methods Transcriptome data of lung tissue samples with COPD patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and Protein-protein interaction (PPI) network were used to identify key genes and interactions. GO enrichment analysis, KEGG analysis, FunRich analysis, and GSEA analysis were used to explore potential biological regulatory mechanisms. CIBERSOFT method for estimating the relative proportions of 22 human immune cells subpopulations. Results A total of 1230 DEGs (660 up-regulated and 570 down-regulated) were identified. WGCNA and PPI selected 8 key genes related to the severity of airflow limitation (GOLD stage), including PRPF19, ATM, CD44, KHDRBS1, RBBP7, VCL, PTEN, and BECN1, which were significantly associated with immune system functions. COPD patients with different GOLD stages have different characteristics of immune cell infiltration, with proportions of T cells (CD8+ T cells, CD4+ memory-resting T cells, CD4+ memory-activated T cells, and gamma delta T cells), B cells (memory B cells) and macrophages (M1 macrophages) upregulated in patients with GOLD stage III-IV. Furthermore, these key genes may regulate multiple immune- and inflammation-related pathways, including Cytokine-cytokine receptor interaction, ECM-receptor interaction, NF-κB signaling pathway, TNF signaling pathway, Chemokine signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Ras signaling pathway, p53 signaling pathway. Conclusions Our study provides new salient genes and immune landscape features associated with COPD, suggesting that these potentially key genes may mediate airflow limitation and disease progression in COPD through immune cell infiltration and immune function regulation.