Deciphering molecular overlaps between COPD and NSCLC subtypes (LUAD and LUSC): An integrative bioinformatics study

Area of Science:

• Bioinformatics
• Genomics
• Molecular Biology

Background:

• Chronic obstructive pulmonary disease (COPD) and non-small-cell lung cancer (NSCLC) are significant global health burdens.
• Emerging evidence suggests shared molecular mechanisms between COPD and NSCLC subtypes, particularly lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).

Purpose of the Study:

• To identify shared differentially expressed genes (DEGs) and molecular pathways between COPD and NSCLC subtypes using an integrative bioinformatics approach.
• To explore potential therapeutic targets and biomarkers for COPD-associated lung cancer.

Main Methods:

• Analysis of gene expression datasets from the Gene Expression Omnibus (GEO) database.
• Identification of DEGs, protein-protein interaction (PPI) networks, and regulatory networks (transcription factors and microRNAs).
• Pathway enrichment analysis (KEGG, GO) and drug-gene interaction analysis.

Main Results:

• Identified 15 shared DEGs between COPD, LUAD, and LUSC, with LUAD showing stronger molecular similarity to COPD than LUSC.
• Key hub genes involved in extracellular matrix (ECM) remodeling and tumor progression were identified (COL10A1, POSTN, SPP1, MMP11, GREM1).
• SP1 was identified as a key transcriptional regulator, and specific miRNAs (hsa-miR-335-5p, hsa-miR-192-5p, hsa-miR-215-5p) were central regulators. Potential drugs include Marimastat, Bosentan, and Minocycline.

Conclusions:

• Shared molecular pathways exist between COPD and NSCLC, with distinct patterns for LUAD and LUSC.
• Identified potential biomarkers (SPP1, POSTN, GREM1) for prognosis and therapeutic targets for drug repurposing in COPD-associated lung cancer.
• This study provides a comprehensive network analysis of TF-miRNA-DEG-drug interactions in COPD-NSCLC.