Purpose Chronic obstructive pulmonary disease (COPD) is a recognized risk factor for lung adenocarcinoma (LUAD), but the molecular mechanisms behind this association are still unclear. This study aims to reveal shared key genes and pathways involved in both COPD and LUAD, and identify potential biomarkers and therapeutic targets. Methods Two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data was performed to evaluate genetic causality. Differential expression analysis was performed on GSE76925 (COPD) and GSE116959 (LUAD), followed by LASSO regression, enrichment analysis, immune cell infiltration analysis, RNA modification analysis, competing endogenous RNA (ceRNA) network construction, and drug sensitivity prediction. Single-cell RNA sequencing data ( GSE270667 , GSE189357 ) were used to explore cell-type-specific expression, and qPCR was performed to validate gene expression in patient blood samples. Results MR confirmed the genetic relationship between COPD and LUAD. Three key genes ( FCRLA , GREM1 , and MMP9 ) were significantly upregulated and involved in immune regulation, extracellular matrix (ECM) remodeling, and the PI3K-Akt signaling pathway. Single-cell analysis revealed that these genes were specifically expressed in B cells, T cells, and monocytes. Multiple omics analyses indicated epigenetic and RNA level regulation. Several candidate drugs have been identified. Conclusion FCRLA, GREM1 , and MMP9 are inflammation-associated genes that may link the pathobiology of COPD and LUAD, and serve as valuable biomarkers with therapeutic potential in high-risk populations.
Li et al. (2026) studied this question.