Definition of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients.

Chiara Cilibrasi,Nicolas Stewart,Georgios Giamas,Nektarios K Mazarakis,Mark Samuels,Giles Critchley,Christos Tolias,Marian Vintu,Thomas Simon,Murat Eravci

doi:10.3390/biomedicines10010125

Abstract

Glioblastoma (GB) is an aggressive type of tumour for which therapeutic options and biomarkers are limited. GB diagnosis mostly relies on symptomatic presentation of the tumour and, in turn, brain imaging and invasive biopsy that can delay its diagnosis. Description of easily accessible and effective biomarkers present in biofluids would thus prove invaluable in GB diagnosis. Extracellular vesicles (EVs) derived from both GB and stromal cells are essential to intercellular crosstalk in the tumour bulk, and circulating EVs have been described as a potential reservoir of GB biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GB diagnosis and follow up. To identify GB specific proteins, sEVs were isolated from plasma samples of GB patients as well as healthy volunteers using differential ultracentrifugation, and their content was characterised through mass spectrometry. Our data indicate the presence of an inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GB diagnosis and, consequently, patients’ prognosis and quality of life.

Highlights

Introduction published maps and institutional affilGlioblastoma multiforme (GB) is defined as a high-grade glioma and the most common intrinsic malignancy of the central nervous system (CNS)
Detailed information about the clinical information on the GB patients enrolled in the study and the molecular features of the tumours can be found in Table 1 and Table S1, respectively
Current GB detection relies on symptomatic presentation of the tumour, magnetic resonance imaging and invasive tissue biopsy, which can delay the identification of the growing malignant mass [8]

Summary

Introduction

Introduction published maps and institutional affilGlioblastoma multiforme (GB) is defined as a high-grade glioma and the most common intrinsic malignancy of the central nervous system (CNS). The fifth edition of the WHO classification of tumours of the CNS, published in 2021, further revised the GB definition as an IDH wild-type tumour presenting one or more of the following three genetic parameters: telomerase reverse transcriptase (TERT) promoter mutation, epidermal growth factor receptor (EGFR) gene amplification and combined gain of entire chromosome 7 and loss of entire chromosome 10 [2]. These molecular identities provide a more accurate prediction of response to treatment and survival rates [3].

Methods

Results

Conclusion