PIP4K2A: A Novel CD8+ T Cell-Related Biomarker Associated with Lung Function Decline in COPD

CD8+ T cells play a pivotal role in Chronic obstructive pulmonary disease(COPD) inflammatory pathogenesis. To elucidate the molecular mechanisms underlying CD8+ T cell involvement in COPD development, this study employed an integrated approach combining bioinformatics analysis with experimental validation to identify CD8+ T cell-associated marker genes, construct a diagnostic model, and evaluate their correlation with pulmonary function in COPD. Lung tissue sequencing data from COPD patients and controls were obtained from the Gene Expression Omnibus(GEO) database. Differential expression analysis was conducted using R on both bulk RNA-seq and single-cell RNA-seq datasets. LASSO regression analysis was subsequently applied to identify hub genes, followed by functional annotation through Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Linear regression analysis assessed correlations between key genes and pulmonary function parameters, with qRT-PCR validation performed on three lung function-associated genes using clinical samples from COPD patients and healthy controls. Our analyses identified seven CD8+ T cell-related genes (CST7, HSPA8, PXN, YPEL5, PIP4K2A, CDKN1B, PIK3IP1) that collectively formed a highly effective diagnostic model. Among these, HSPA8, PIP4K2A, and YPEL5 demonstrated significant correlations with impaired lung function in COPD patients. qRT-PCR validation confirmed PIP4K2A expression patterns in clinical samples, consistent with microarray data. These findings establish CD8+ T cell-associated biomarkers for COPD, with PIP4K2A expression showing particular relevance to lung function decline, thereby providing new molecular insights into CD8+ T cell-mediated mechanisms in COPD pathogenesis.