Multidimensional analysis of matched primary and recurrent glioblastoma identifies contributors to tumor recurrence influencing time to relapse

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...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2024-10, Vol.84 (1), p.45-58
Main Authors: Shekarian, Tala, Ritz, Marie-Françoise, Hogan, Sabrina, Martins, Tomás A, Schmassmann, Philip, Gerber, Alexandra, Roux, Julien, Kaymak, Deniz, Durano, Célia, Burger, Bettina, Matter, Matthias, Hutter, Gregor
Format: Article
Language:English
Subjects:
Adult
Aged
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Female
Glioblastoma - genetics
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
Male
Middle Aged
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - pathology
Original
Citations: Items that this one cites
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Summary: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.
ISSN:0022-3069
1554-6578
1554-6578
DOI:10.1093/jnen/nlae108