BIOM-12. LIQUID BIOPSY FOR GLIOBLASTOMA: PLASMA EXTRACELLULAR VESICLES FOR TUMOR DIAGNOSIS, MONITORING, AND PATIENT STRATIFICATION

Abstract INTRODUCTION Despite recent advances, the therapies available for glioblastoma (GBM) still fall short of delivering a cure. Meaningful progress now rests on precision-medicine approaches that depend on robust biomarkers to diagnose, characterize, and monitor the tumor while supporting patient stratification. Unfortunately, an effective liquid biopsy able to fulfill these roles for GBM has yet to be realized. This study tests plasma extracellular vesicles (EVs) as non-invasive GBM biomarkers. METHODS EVs were isolated from plasma by SEC and characterized. EVs concentration and size were quantified with TRPS. Baseline EVs levels from 62 pre-operative GBM patients were compared with two control groups: 79 healthy volunteers and 50 patients harboring other brain malignancies that radiologically mimic GBM. Serial plasma samples for longitudinal EV analysis were collected from 44 of the GBM patients. Surface-marker profiling and proteomic characterization of EVs were performed by mass spectrometry in a subset of plasma specimens (27 GBM patients and 38 healthy controls) RESULTS Plasma EV concentration and mean size significantly differ between GBM patients and controls. Following surgery, both parameters become comparable to healthy controls but increase again upon tumor recurrence. EVs size and concentration effectively distinguish GBM from control groups (C1 and C2), achieving near-perfect AUC values. EV size is a predictive biomarker for response to radio- and chemotherapy. Longitudinal monitoring of EV concentration reflects GBM progression, even preceding radiological evidence on MRI. Proteomic analysis identified over 2,000 proteins across all samples, with 117 upregulated in GBM patients and enriched in complement cascade pathways. CONCLUSIONS Monitoring circulating EVs offers a highly sensitive and specific, non-invasive tool for the differential diagnosis of GBM, patient stratification, and longitudinal follow-up. Integrating EV concentration, size, and proteomic signatures yields a robust biomarker panel that can track disease dynamics over time, underscoring the promise of liquid-biopsy strategies in routine GBM management.