Extracellular vesicle proteomic expression is influenced by mining tenure in former uranium miners.

ABSTRACT:

Background

Chronic exposure to uranium (U) rich environments poses significant health risks, yet the molecular mechanisms underlying these effects remain poorly understood. Extracellular vesicles (EVs) are membrane-bound vesicles that transfer multiple biomolecules between cells and can regulate cellular function.

Objective

To determine whether U-mining tenure is associated with specific alterations in serum-derived EV proteomic and plasma cytokine profiles among former U-miners, and to assess the potential of EV-derived proteins as robust biomarkers of chronic U-exposure relative to canonical cytokines.

Methods

Serum and plasma samples were obtained from 39 former U-miners. Small and large EVs were isolated via differential ultracentrifugation and characterized by nanoparticle tracking and western blotting. EV proteomic profiles were analyzed using liquid chromatography-tandem mass spectrometry. Plasma cytokines were quantified using multiplex immunoassays. Age-adjusted linear regression was used to assess associations with mining tenure, and pathway enrichment analysis was performed on significant EV proteins.

Results

Eight small-EV and four large-EV proteins significantly correlated with mining tenure after age adjustment. Notably, Complement C1r subcomponent and Vitamin K-dependent protein S, and Fibrinogen alpha chain exhibited strong inverse correlations. Enrichment analyses highlighted immune-related and extracellular matrix pathways. Six cytokines were initially associated with mining tenure but lost significance after age adjustment. In contrast, EV protein associations appeared more robust for this confounding, underscoring their potential as exposure biomarkers.

Conclusions

Serum EV-derived protein signatures were nominally associated with U-mining tenure independent of age, whereas cytokine profiles were confounded by age. These findings suggest that EV-derived proteins may provide sensitive biomarkers for monitoring long-term health effects of U-exposure, which warrants further investigation in larger cohorts.

SUBMITTER: Oh M 

PROVIDER: S-EPMC12457906 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature