Fire-Smoke InducedProtein Alterations in Firefighters'Body Fluids Identify Prognostic Pan-cancer Biomarkers

Abstract Firefighters are routinely exposed to complex mixtures of toxicants during fire suppression, and growing evidence links these exposures to elevated cancer risk. Proteomic profiling provides a sensitive means to detect early molecular alterations associated with such occupational hazards. In this study, we performed a comparative label-free proteomic analysis of paired serum (n = 42) and urine (n = 50) samples collected from firefighters at baseline and within 24 h postfire suppression. We identified and quantified 330 protein groups in serum and 1085 in urine. PLS-DA of total protein abundance showed clear separation between pre- and postexposure samples in both biofluids, indicating exposure-related proteomic changes. Volcano plot analysis further revealed multiple significantly altered proteins in both biofluids, wherein the urine-proteome showed a broader range of differential expressions. Proteins altered in at least 70% of samples were subjected to pathway enrichment analysis, identifying associations with several diseases, including small-cell lung cancer. Protein–protein interaction analysis revealed highly interconnected cancer-related networks involving LAMA4, LAMC1, VWF, and B2M. These findings suggest urine is a sensitive matrix for detecting acute exposure effects, while serum provides complementary systemic information. Integrating both biofluids into NFPA 1582-guided surveillance may enhance occupational health monitoring and support early cancer detection and prevention in firefighters.