Molecular signatures under hexavalent chromium, particulate matter 2.5, and cigarette smoking exposures.

Exposure to air environment pollutants is one of the leading causes of lung cancer. To date, no relevant studies have compared the molecular signatures under exposure to lung cancer-related public air pollution, occupational exposure and personal pollutants, including hexavalent chromium [Cr(VI)], particulate matter 2.5 (PM2.5) and cigarette smoking. In this study, we conducted the Weighted gene co-expression network analysis (WGCNA) to identify the key modules under pollutant exposure, and used Mfuzz analysis to discover dose- or time-dependent gene sets. Pathway enrichment analysis and differentially expressed gene analysis were utilized to identify pollutant-induced signature genes. The results showed that the PI3K–AKT pathway is the most significantly upregulated pathway in Cr(VI) exposure, with significant upregulation observed in the genes CCND1, GDNF, IL7R, ITGA4, KIT, and PRKAA2. We found that PM2.5 activated the growth factor receptor binding pathway, significantly upregulating the expression of the proteins IL1A, TGFA and PDGFA on this pathway with increasing treatment time and dosage.Furthermore, cigarette smoking exposure activated MAPK cascade pathway and growth factor activity and the key genes ACTA2, FGF2, ROR2, FGF21, INHBE and MDK levels were elevated with increasing exposure duration. Our study delineates the molecular landscapes under three environmental pollutants and reveals the molecular mechanisms underlying the induction of malignant cell transformation by different environmental pollutants.