Background: Indoor radon is a significant risk factor for the development of LC. This study aimed to identify potential biomarkers for LC risk in high background radiation areas using a metabolomics approach (UHPLC-HRMS). Methods: Based on the indoor radon activity concentration measurements in the Kong Khaek subdistrict, serum samples were collected from 45 nonsmoker or former smoker participants, comprising 15 LC patients and 30 matched healthy controls (low- and high-radon groups, respectively). Results: A total of 90 and 111 differential metabolites were identified in the LC group compared with the low- and high-radon groups, respectively, using criteria such as a variable importance in projection (VIP) of >1, a fold change (FC) of >1 or <0.5, and a p value of <0.05. Receiver operating characteristic (ROC) curves (an AUC of ≥ 0.9) indicated that 30 and 21 of these metabolites had the potential to serve as biomarkers of LC development in the low- and high-radon groups, respectively. The KEGG pathway enrichment analysis suggested that D-sphingosine may have been a candidate biomarker associated with LC in both groups. Conclusions: Overall, this study provides new insights into metabolic biomarkers for screening LC development in high-risk individuals with prolonged exposure to indoor radon. Further large-scale studies are needed to validate our results.
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