High-Grade Gliomas from Subventricular Zone: Proteomic Drivers of Aggressiveness Using Fluorescence-Guided Multiple Sampling.

Abstract

High-grade gliomas (HGGs) are among the most aggressive brain tumors and are characterized by dismally low median survival time. Of the many factors influencing the survival of patients with HGGs, proximity to the subventricular zone (SVZ) is one of the key influencers. In this context, 5-amino levulinic acid fluorescence-guided multiple sampling (FGMS) offers the prospect of understanding patient-to-patient molecular heterogeneity driving the aggressiveness of these tumors. Using high-resolution liquid chromatography-mass spectrometry (MS)/MS proteomics for HGGs from seven patients (four SVZ associated and three SVZ nonassociated), this study aimed to uncover the mechanisms driving the aggressiveness in SVZ-associated (SVZ+) HGGs. Differential proteomics analysis revealed significant dysregulation of 11 proteins, of which 9 proteins were upregulated and 2 were downregulated in SVZ+ HGGs compared to SVZ-non-associated (SVZ-) HGGs. The gene set enrichment analysis (GSEA) of the proteomics dataset revealed enrichment of MYC targets V1 and V2, G2M checkpoints, and E2F targets in SVZ+ HGGs. With GSEA, we also compared the pathways enriched in glioma stem cell subpopulations and observed a similar expression trend for most pathways in our data. In conclusion, this study reveals new and emerging insights on pathways that may potentially contribute to greater aggressiveness in SVZ+ HGGs. Future studies using FGMS in larger cohorts are recommended to help uncover the proteomics and molecular basis of aggressiveness and stemness in HGGs.