Abstract

Abstract BACKGROUND Gliomas are the second most frequent primary brain tumor. Since 2016 gliomas are classified according to histological, and molecular features such as IDH status and 1p19q codeletion. Recently oncological research has focused on liquid biopsies to reduce the need for invasive diagnostic tests. Cerebrospinal fluid (CSF) is the principal source of brain tumor biomarkers. Modern technologies currently allow us to analyze proteomic and metabolomic tumor profiles, in order to find new biomarkers without being constrained by a priori hypothesis. Several data from the literature also suggests that inflammatory cells and cytokines in tumors contribute to tumor growth, progression and immunosuppression. The possibility of simultaneously testing different inflammatory molecules on the biological fluids could lead to the identification of new biological markers with prognostic and predictive value for treatment response. STUDY OBJECTIVES - Identification of protein and/or lipid biomarkers specific to the glioma subgroup among those under analysis. - Identification of tumor group- and subgroup-specific CSF and/or serum inflammatory biomarkers among those tested. - Correlation of biomarkers with Progression Free Survival (PFS), Overall Survival (OS). ELIGIBILITY CRITERIA - Patients with a radiological suspected diagnosis of glioma eligible for surgery. - Age ≥ 18 years. - Availability of histological samples, CSF, blood and urine. - Patients with unconfirmed histological diagnosis of glioma will be excluded. - Patients who have never received any systemic or local treatment for CNS diseases. STUDY DESIGN This is a prospective monocentric study involving mass spectrometry analysis for characterization of proteins and metabolites and ELISA analysis for the characterization of different cytokines in parallel anonymized biological samples consisting of tumor tissue, CSF, blood and urine from glioma patients, divided into three different molecular subtypes: 1p19q codelet/IDH mutated, 1p19q non-codelet/IDH mutated and 1p19q non-codelet/IDH wt. Biological samples will be taken at surgery, at 24–48 h after surgery and every 3 months up to 1 year. The control group will include patients with subarachnoid hemorrhage or hydrocephalus, either undergoing external ventricular shunting or undergoing ventricular catheter placement/revision surgery. STUDY ANALYSIS Data interpretation will be based on a statistical analysis of the data, applying tools such as Principal Component Analysis (PCA) Weighted Correlation Network Analysis (WGNCA), Multiple Venn Diagram, T-Test, ANOVA, Clustering and Gene Ontology Enrichment, non-parametric Mann-Whitney test. For the assessment of clinical outcome, survival curves will be compared between different groups of patients who share a similar protein/metabolomic/inflammatory profile.

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