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Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients

医学 生物标志物 细胞外小泡 胶质母细胞瘤 肿瘤科 癌症研究 化学 生物 生物化学 细胞生物学
作者
Franz Ricklefs,Kathrin Wollmann,Amanda Salviano‐Silva,Richard Drexler,Cécile L. Maire,Michael G. Kaul,Rudolph Reimer,Ulrich Schüller,Sarina Heinemann,Katharina Kolbe,Tobias Mummert,Markus Glatzel,Sven Peine,Jens Gempt,Manfred Westphal,Lasse Dührsen,Katrin Lamszus
出处
期刊:Neuro-oncology [Oxford University Press]
卷期号:26 (7): 1280-1291 被引量:7
标识
DOI:10.1093/neuonc/noae068
摘要

Abstract Background Extracellular vesicles (EVs) obtained by noninvasive liquid biopsy from patient blood can serve as biomarkers. Here, we investigated the potential of circulating plasma EVs to serve as an indicator in the diagnosis, prognosis, and treatment response of glioblastoma patients. Methods Plasma samples were collected from glioblastoma patients at multiple timepoints before and after surgery. EV concentrations were measured by nanoparticle tracking analysis and imaging flow cytometry. Tumor burden and edema were quantified by 3D reconstruction. EVs and tumors were further monitored in glioma-bearing mice. Results Glioblastoma patients displayed a 5.5-fold increase in circulating EVs compared to healthy donors (P < .0001). Patients with higher EV levels had significantly shorter overall survival and progression-free survival than patients with lower levels, and the plasma EV concentration was an independent prognostic parameter for overall survival. EV levels correlated with the extent of peritumoral fluid-attenuated inversion recovery hyperintensity but not with the size of the contrast-enhancing tumor, and similar findings were obtained in mice. Postoperatively, EV concentrations decreased rapidly back to normal levels, and the magnitude of the decline was associated with the extent of tumor resection. EV levels remained low during stable disease, but increased again upon tumor recurrence. In some patients, EV resurgence preceded the magnetic resonance imaging detectability of tumor relapse. Conclusions Our findings suggest that leakiness of the blood-brain barrier may primarily be responsible for the high circulating EV concentrations in glioblastoma patients. Elevated EVs reflect tumor presence, and their quantification may thus be valuable in assessing disease activity.
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