Proteome profiling of extracellular vesicles from neurosurgical aspirates identifies CCT6A as a potential glioblastoma biomarker with prognostic significance

ABSTRACT: Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth rates and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000nm membranous particles) influence the microenvironment to mediate tumour aggressiveness and carry oncogenic cargo across the blood-brain-barrier into the circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumours in situ. Neurosurgical aspirates are rich sources of EVs, isolated directly from glioma microenvironments. Quantitative LC-MS/MS compared EV proteomes enriched from glioblastoma (n=15) and glioma grade II-III (n=7) aspirates and identified 298 differentially-abundant proteins (p-value<0.00496). Along with previously reported glioblastoma-associated biomarkers, levels of all eight subunits of the key molecular chaperone, T-complex protein 1 Ring complex (TRiC), were higher in glioblastoma-EVs, including CCT2, CCT3, CCT5, CCT6A, CCT7 and TCP1 (p<0.00496). Analogous increases in TRiC transcript levels and DNA copy numbers were detected in silico; CCT6A had the greatest induction of expression and amplification in glioblastoma and showed a negative association with survival (p=0.006). CCT6A is co-localised with EGFR at 7p11.2, with a strong tendency for co-amplification (p<0.001). Immunohistochemistry corroborated the CCT6A proteomics measurements and indicated a potential link between EGFR and CCT6A tissue expressions. Putative EV-biomarkers described here should be further assessed in peripheral blood.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Brain Glioblastoma Multiforme,Glioblastoma,Brain Cancer

SUBMITTER: Susannah Hallal  

LAB HEAD: Kimberley Louise Kaufman

PROVIDER: PXD010247 | Pride | 2022-03-01

REPOSITORIES: pride