Article
Circulating extracellular vesicles as a tool for diagnosis, prognosis and monitoring in Glioma
Zirkulierende extrazelluläre Vesikel als ein Instrument für die Diagnose, Prognose und Überwachung bei Gliomen
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Authors
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Franz Lennard Ricklefs
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Kathrin Wollmann
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Richard Drexler
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Manfred Westphal
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Katrin Lamszus
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Lasse Dührsen
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Extracellular vesicles (EVs) represent a population of lipid bilayer nanoparticles released by all cell types, including tumor cells, and have recently attracted attention as mediators of intercellular communication. EVs harbor tumor-specific nucleic acids and proteins, cross the blood-brain barrier, and therefore can serve as a noninvasive source for liquid biopsy. To date, MRI images have been the established method for monitoring treatment efficacy in brain tumor patients. Given the urgent need for a reliable biomarker for treatment monitoring of glioblastoma patients, we investigated the potential of pure EV count for diagnosis, prognosis, and treatment monitoring in gliomas.
Methods: We collected plasma samples as well as differential blood counts from glioblastoma (n=101) before, as well as on the first and fourth day after, microsurgical tumorresection. Follow-up samples were obtained every 3 months. Additionally, we analyzed a group of healthy donors (n=29). EVs were isolated by Ultracentrifugation and the plasma concentration was measured by Nanoparticle Tracking Analysis (NTA). Tumor burden was measured on T1-weighted and FLAIR MRI images. Clinical characteristics were prospectively recorderd and retrospectively.
Results: Prior to surgery, the level of circulating EVs in glioblastoma is elevated, distinguishing them from healthy controls (5-fold increase in GBM; p < 0.0001). Circulating EVs counts correlated only with FLAIR hyperintensity and with no other MRI or blood-based parameter. Dichotomisation of GBM patients in EVhigh and low revealed a significant overall survival and progression free survival benefit for EVlow patients (p=0.004). After surgery, circulating EVs decreased significantly (5-fold, p<0.0001). A massive drop in EVs was associated with a more radical surgical resection (p < 0.05). Interestingly, at the time of tumor recurrence, the number of circulating EVs increased again in all patients during a follow-up period of 9 months.
Conclusion: Our findings highlight the potential of circulating EVs as a biomarker tool for diagnosis, prognosis and treatment monitoring in GBM patietns, as they seem to reflect the presence of a tumor mass and thus may assist in clinical decision making.
Figure 1 [Fig. 1]
