Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a 'liquid gold' biopsy

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 wh...

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Bibliographic Details
Published in:British journal of cancer 2024-03, Vol.130 (5), p.836-851
Main Authors: Hallal, Susannah M, Tűzesi, Ágota, Sida, Liam A, Xian, Elissa, Madani, Daniel, Muralidharan, Krishna, Shivalingam, Brindha, Buckland, Michael E, Satgunaseelan, Laveniya, Alexander, Kimberley L
Format: Article
Language:English
Subjects:
Biomarkers
Biomarkers - metabolism
Biopsy
Chromatography, Liquid - methods
Extracellular vesicles
Extracellular Vesicles - metabolism
Glioblastoma
Glioblastoma - pathology
Humans
Liquid Biopsy
Liquid chromatography
Mass spectroscopy
Nanoparticles
Proteomes
Proteomics
Proteomics - methods
Tandem Mass Spectrometry
Tumors
Ultracentrifugation
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Summary: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. 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). 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). 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-023-02548-9