Dynamic characteristics of metabolism and small extracellular vesicles during malignant transformation of BEAS-2B cells induced by coal tar pitch extract

Lung cancer poses a significant global burden with rising morbidity and mortality. Coal tar pitch-induced lung cancer is an occupational disease where early detection is crucial but challenging due to unclear pathogenesis. We established a malignant transformation model using BEAS-2B cells treated with coal tar pitch extract (CTPE). Macro-and micro-observations showed CTPE-induced alterations, including changes in cell morphology, enhanced proliferation and migration abilities, upregulated EGFR expression, modified levels of CYP1A1 and GSTM1 metabolizing enzymes, and a transition towards a mesenchymal phenotype. These findings strongly suggest that the cells have undergone malignant transformation. Metabolomics analysis revealed changes in 1120 metabolites, with 31 co-expressed, mainly in energy and amino acid metabolism. Small extracellular vesicles (SEVs) concentrations and EGFR levels were significantly altered. Correlation analysis identified a relationship between these biomarkers, implying their potential significance as early events in the initiation and progression of lung cancer. These findings provide valuable insights and a rationale for lung cancer screening and mechanistic investigations, thereby contributing to a deeper understanding of the disease.