Proteomic Profiling of Cerebrospinal Fluid and its EVs from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, Towards Precision Oncology

ABSTRACT: Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a good prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from 24 PA, cerebral hemorrhage (CH, non-tumor controls), or medulloblastoma (MB, unrelated tumoral controls) patients. 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which expressed in the unprocessed total, and its microvesicle (Mv), and exosome (Ex) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western Blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers to discriminate among pilocytic astrocytoma, and unrelated tumoral (MB) or non-tumoral conditions, in all the fractions examined, proposed to be prospectively validated in the plasma for translational medicine applications.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Martina Bartolucci  

LAB HEAD: Andrea Petretto

PROVIDER: PXD050589 | Pride | 2024-05-23

REPOSITORIES: Pride