Cigarette Smoke-Induced Transcriptomic Alterations and Angiogenesis in Non-Small Cell Lung Cancer: An Integrative Analysis

Background & Objectives: Cigarette smoke is a major risk factor for non-small cell lung cancer (NSCLC) and plays a pivotal role in tumor initiation and angiogenesis. This study aimed to elucidate the molecular mechanisms through which cigarette smoke influences angiogenesis in NSCLC by integrating transcriptomic data, with a particular emphasis on the regulatory role of microRNA-1 (miR-1) and its downstream targets. Materials & Methods: We analyzed the Gene Expression Omnibus (GEO) dataset GSE290190, comprising gene expression profiles from 18 samples with different smoking statuses (9 normal and 9 tumor tissues). Differential expression analysis, Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) enrichment, and Protein–Protein Interaction (PPI) network analysis were conducted to identify critical genes and signaling pathways. Statistical analyses were employed to determine differentially expressed genes (DEGs) and to assess their biological relevance. Results: Differential expression analysis identified 2,449 DEGs between normal and tumor tissues, with significant enrichment in angiogenesis, cell cycle regulation, and DNA repair pathways. Key angiogenesis-related genes—VEGFC, FGF2, and ANGPT1—were recognized as direct targets of miR-1. GSEA and GO analyses revealed marked alterations in biological processes such as chromosome segregation, mitotic nuclear division, and extracellular matrix organization. PPI network analysis identified E2F7, PLK1, and TOP2A as hub genes, suggesting their potential roles as key regulators in cell cycle progression and tumorigenesis. Conclusion: This study highlights the transcriptomic heterogeneity of NSCLC and proposes miR-1 and its downstream targets—VEGFC, FGF2, and ANGPT1—as promising biomarkers and therapeutic targets. However, further validation using larger datasets and functional assays is essential to confirm these findings and facilitate their clinical translation