Breast cancer is linked to changes in the urinary extracellular vesicle proteome

Breast cancer (BC) remains a leading cause of morbidity and mortality worldwide. Early detection remains the most effective strategy for improving prognosis. We explored the urinary extracellular vesicle (uEV) proteome for changes linked to BC which could also be potential biomarkers. Urine samples were collected from 20 participants across four groups (n = 5 each): newly diagnosed BC patients, benign breast disease (BBD) patients, individuals with breast cancer symptoms (symptom control, SC), and age-matched healthy controls (HC). EVs were isolated using size exclusion chromatography and extracted proteins were analysed using a GeLC proteomic approach. Proteins were identified and quantified using Proteome Discoverer and further analysed using MetaboAnalystR, Funrich and Metascape. A total of 256 proteins were identified from the uEV preparations. BC comparisons with BBD, SC and HC identified 7 proteins differentially expressed proteins (DEP); SERPINB1 -- Serpin family B member 1, LCN1 -- Lipocalin 1, SIRPA -- Signal regulatory protein alpha, ACTB -- Actin, beta, YWHAZ --Tryptophan 5-monooxygenase activation protein zeta, Ig JCHAIN and APOA1 -- Apolipoprotein A1. Receiver Operator Characteristic (ROC) curve assessments suggested that each DEP protein had an area under the curve (AUC) of > 0.8. These findings highlight EV-derived proteins as promising non-invasive biomarkers for breast cancer detection, warranting further validation in larger cohorts.