Multidimensional Analysis of Matched Primary and Recurrent Glioblastoma Identifies Contributors to Tumor Recurrence Influencing Time to Relapse

Overview

Journal J Neuropathol Exp Neurol

Publisher Oxford University Press

Specialties Neurology
Pathology

Date 2024 Oct 18

PMID 39423857

Authors

Tala Shekarian

Marie-Francoise Ritz

Sabrina Hogan

Tomas A Martins

Philip Schmassmann

Alexandra Gerber

Julien Roux

Deniz Kaymak

Celia Durano

Bettina Burger

Matthias Matter

Gregor Hutter

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. This study aimed to characterize longitudinal tumor changes in order to find potentially actionable targets to prevent GBM relapse. We extracted RNA and proteins from fresh frozen tumor samples from patient-matched IDHwt WHO grade 4 primary (pGBM) and recurrent (rGBM) tumors for transcriptomics and proteomics analysis. A tissue microarray containing paired tumor samples was processed for spatial transcriptomics analysis. Differentially expressed genes and proteins between pGBM and rGBM were involved in synapse development and myelination. By categorizing patients into short (STTR) and long (LTTR) time-to-lapse, we identified genes/proteins whose expression levels positively or negatively correlated with TTR. In rGBM, expressions of Fcγ receptors (FCGRs) and complement system genes were negatively correlated with TTR, whereas expression of genes involved in DNA methylation was positively correlated with TTR. Spatial transcriptomics of the tumor cells showed enrichment of oligodendrocytes in rGBM. Besides, we observed changes in the myeloid compartment such as a switch from quiescent to activated microglia and an enrichment in B and T cells in rGBM with STTR. Our results uncover a role for activated microglia/macrophages in GBM recurrence and suggest that interfering with these cells may hinder GBM relapse.

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