Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy
Menée à partir de 50 échantillons urinaires collectés auprès de 24 patients atteints d'un glioblastome, cette étude met en évidence l'intérêt des vésicules extracellulaires urinaires pour identifier et mesurer des biomarqueurs associés à la tumeur
Background : Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30–1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as a simple and non-invasive liquid biopsy approach for measuring glioblastoma-associated biomarkers.
Methods : Fifty urine specimens (15–60 ml) were collected from 24 catheterised glioblastoma patients immediately prior to primary (n = 17) and recurrence (n = 7) surgeries, following gross total resection (n = 9), and from age/gender-matched healthy participants (n = 14). EVs isolated by differential ultracentrifugation were characterised and extracted proteomes were analysed by high-resolution data-independent acquisition liquid chromatography tandem mass spectrometry (DIA-LC-MS/MS).
Results : Overall, 6857 proteins were confidently identified in urinary-EVs (q-value
≤
0.01), including 94 EV marker proteins. Glioblastoma-specific proteomic signatures were determined, and putative urinary-EV biomarkers corresponding to tumour burden and recurrence were identified (FC
≥
| 2 | , adjust p-val
≤
0.05, AUC > 0.9).
Conclusion : In-depth DIA-LC-MS/MS characterisation of urinary-EVs substantiates urine as a viable source of glioblastoma biomarkers. The promising ‘liquid gold’ biomarker panels described here warrant further investigation.
British Journal of Cancer , article en libre accès, 2024