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Journal Articles Cancer Cell Year : 2023

Transcriptome analysis reveals tumor microenvironment changes in glioblastoma

Wouter Coppieters
  • Function : Author
Latifa Karim
  • Function : Author
Manon Deckers
  • Function : Author
Melissa Kerkhof
  • Function : Author
Ann Hoeben
  • Function : Author
Slávka Lukacova
  • Function : Author
Giuseppe Lombardi
  • Function : Author
Sieger Leenstra
  • Function : Author
Monique Hanse
  • Function : Author
Ruth E.M. Fleischeuer
  • Function : Author
Colin Watts
  • Function : Author
Thierry Gorlia
  • Function : Author
Vassilis Golfinopoulos
  • Function : Author
Vincent Bours
  • Function : Author
Martin J van den Bent
  • Function : Author
Pim J French
  • Function : Author
  • PersonId : 1368593

Abstract

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells.
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hal-04523610 , version 1 (27-03-2024)

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Youri Hoogstrate, Kaspar Draaisma, Santoesha A Ghisai, Levi van Hijfte, Nastaran Barin, et al.. Transcriptome analysis reveals tumor microenvironment changes in glioblastoma. Cancer Cell, 2023, 41 (4), pp.678-692.e7. ⟨10.1016/j.ccell.2023.02.019⟩. ⟨hal-04523610⟩
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