Integrated transcriptomic and functional analysis reveals overlapping pathways in lung adenocarcinoma and chronic obstructive pulmonary disease

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, with chronic obstructive pulmonary disease (COPD) identified as a major risk factor. However, the molecular overlap between LUAD and COPD remains poorly understood. This study aimed to identify shared hub genes and to evaluate their functional significance in LUAD. Differential gene expression analysis was conducted using two LUAD (GSE19188, GSE18842, and GSE31210) and two COPD (GSE76925, GSE57148, and GSE137557) datasets from the Gene Expression Omnibus (GEO) database. Common hub genes were identified by Venn diagram intersection of the top 3,000 DEGs per dataset. Validation was performed via RT-qPCR in LUAD (A549 and H1299) and COPD cell models. Additional transcriptomic and proteomic validations were done using GSCA, OncoDB, and HPA databases. miRNA–mRNA interactions were predicted using TargetScan and validated by TaqMan RT-qPCR. Functional assays, including CCK-8, colony formation, and wound healing, were performed after overexpression of SYNE1 and SULT1A1 in LUAD cell lines. Four common hub genes, including SYNE1, SULT1A1, FAM76A, and COL10A1 were identified in both LUAD and COPD. SYNE1, SULT1A1, and FAM76A were significantly downregulated, while COL10A1 was upregulated. miRNAs targeting these genes (miR-22-3p, miR-17-3p, miR-455-3p.2, and miR-1297) were significantly upregulated in LUAD and COPD models. Immune correlation analysis revealed associations between hub gene expression and immune subtypes, immune checkpoint regulators, and drug resistance. Functional assays demonstrated that overexpression of SYNE1 and SULT1A1 suppressed proliferation, colony formation, and migration in LUAD cells. Immune correlation analysis revealed associations between hub gene expression and immune subtypes, immune checkpoint regulators, and drug resistance. This study identifies shared molecular signatures between LUAD and COPD.