Identification of Novel Protein Biomarkers for Early Detection of Radon-Induced Lung Cancer: A Comparative Study in...

Background: Radon exposure is the second most important risk factor for lung cancer after tobacco smoking and represents a significant but often underestimated public health problem. Due to the absence of specific clinical manifestations at early stages, the identification of molecular biomarkers reflecting early radon-induced carcinogenic processes is of particular importance. The aim of this study was to identify protein biomarkers associated with radon exposure in lung cancer patients residing in settlements of the Akmola and North Kazakhstan regions of Kazakhstan. Methods: Indoor radon exposure was assessed using CR-39 detectors to measure radon concentrations in residential dwellings during summer and autumn periods. The study included 57 lung cancer patients and 73 control subjects residing in areas characterized by varying levels of radon exposure. Plasma samples were collected and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins associated with lung cancer and radon exposure. Statistical analyses were performed to evaluate differences between groups and associations between radon exposure and molecular biomarkers. Results: Seasonal variability in indoor radon concentrations was observed, with several settlements demonstrating levels exceeding international reference values. Proteomic analysis identified multiple proteins differentially expressed between lung cancer patients and controls, as well as between radon-exposed and non-exposed lung cancer patients. Several proteins involved in inflammation, lipid metabolism, oxidative stress, and immune regulation pathways demonstrated significant differences in expression levels, suggesting potential associations with radon-induced carcinogenic mechanisms. LC-MS/MS proteomic profiling identified multiple differentially expressed proteins associated with lung cancer and radon exposure after false discovery rate correction. Proteins involved in inflammation, oxidative stress, immune regulation, and lipid metabolism, including ORM2, AZGP1, PRDX2, IRF7, and APOC3, demonstrated significant expression differences between radon-exposed and low-exposure groups. Conclusions: The identified protein biomarkers demonstrated significant associations with both radon exposure and lung cancer status, indicating their potential relevance for early detection and risk assessment of radon-induced lung cancer. The integration of environmental exposure assessment with proteomic profiling may provide new insights into the molecular mechanisms of radon-associated carcinogenesis and support the development of preventive strategies.