Clinical significance of extracellular vesicles in plasma from glioblastoma patients

Daniela Osti, Massimiliano Del Bene, Germana Rappa, Mark Santos, Vittoria Matafora, Cristina Richichi, Stefania Faletti, Galina V. Beznoussenko, Alexandre Mironov, Angela Bachi, Lorenzo Fornasari, Daniele Bongetta, Paolo Gaetani, Francesco DiMeco, Aurelio Lorico, Giuliana Pelicci

Research output: Contribution to journalArticle

Abstract

Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. Experimental Design: Plasma from healthy controls (n ¼ 33), patients with GBM (n ¼ 43), and patients with different central nervous system malignancies (n ¼ 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. Results: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. Conclusions: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

Original languageEnglish
Pages (from-to)266-276
Number of pages11
JournalClinical Cancer Research
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Osti, D., Bene, M. D., Rappa, G., Santos, M., Matafora, V., Richichi, C., Faletti, S., Beznoussenko, G. V., Mironov, A., Bachi, A., Fornasari, L., Bongetta, D., Gaetani, P., DiMeco, F., Lorico, A., & Pelicci, G. (2019). Clinical significance of extracellular vesicles in plasma from glioblastoma patients. Clinical Cancer Research, 25(1), 266-276. https://doi.org/10.1158/1078-0432.CCR-18-1941