Molecular mechanisms of inhalable iron-containing particles driving lung carcinogenesis through the

Background: Iron, an essential trace element ubiquitously present in living organisms, is integral to various biological processes. Epidemiological studies have shown an elevated relative risk of lung cancer among male individuals with occupational exposure to high iron environments (such as those working near iron and steel production facilities). This suggests that respirable iron-containing particulate matters (RICPMs) may pose a potential carcinogenic risk; nevertheless, the underlying mechanisms remain poorly understood. The objective of this study is to explore the potential carcinogenic mechanisms of RICPM through integrative bioinformatics analyses combined with experimental validation. Methods: Sequencing data of a welding fume-exposed mouse model (GSE34056) were downloaded from the Gene Expression Omnibus (GEO) database. Ferroptosis-related genes were retrieved from The Cancer Genome Atlas-lung adenocarcinoma (TCGA-LUAD), Molecular Signatures Database (MSIGDB), and GeneCards® Human Gene Database (GENECARDS) databases. Key genes were screened and analyzed for expression profiles, single-gene pan-cancer relevance, single-gene Gene Set Enrichment Analysis (GSEA), and drug sensitivity. Experimental validations included measurements of reactive oxygen species (ROS), lipocalin-2 ( Results: Nano-Fe Conclusions: The findings elucidate the potential carcinogenic pathways of RICPM and underscore