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Pilot proteomics study suggests elevated tumorigenesis-promoting biomarkers in healthy adults after air pollution exposure

Ding, V.; Lu, D.; Ji, Y.; Johnson, M. M.; Haddad, F.; Kim, J. B.; Horne, B. D.; Park, J.-A.; Nadeau, K. C.; Desai, M.; Maecker, H. T.

2025-09-14 occupational and environmental health
10.1101/2025.09.12.25335654 medRxiv
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ObjectivesRecent studies have shown that immune and cardiometabolic biomarker levels increased in individuals exposed to ambient air pollution. We sought to explore the feasibility of identifying a pollution exposure signature using the Olink Explore platform in a small, pilot cohort of firefighters and age-matched controls in the Bay Area. MethodsDemographics and plasma samples were collected at two study visits, one following the resolution of Californias record-setting 2020 wildfires and another in the spring of 2021. Age-matched samples were processed on the same plate, with 10 repeated on a second plate for assessing inter-plate variation. For comparing firefighter profile with healthy controls, we analyzed Olink proteomics data under multiple approaches for feature selection, including LASSO (the least absolute shrinkage and selection operator), elastic net, and PLS-DA (partial least squares discriminant analysis). In addition, we selected 67 biomarkers related to well-defined pathways for targeted analyses, whereas 1463 unique assays were considered for untargeted analyses. ResultsOur analysis found that levels of angiopoietin 1 and hydroxyacylglutathione hydrolase were consistently higher in firefighters compared to controls. Moreover, matrix metalloproteinase-1, a protein that promotes tumorigenesis, was higher at the visit with greater acute exposure. Fifteen other key biomarkers were jointly identified under untargeted and targeted approaches. When comparing targeted biomarkers in firefighters by level of exposure using a mixed effects regression model, 10 were found to be numerically higher in firefighters with high exposure. ConclusionsThese analyses demonstrate the potential utility of large-scale plasma proteomics in identifying a pollution exposure signature.

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