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

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.

SUBMITTER: Cilibrasi C

PROVIDER: S-EPMC8773644 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6-15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins-namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112-showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).

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

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