Expression Profiling of Primary and Recurrent Glioblastomas Reveals a Reduced Level of Pentraxin 3 in Recurrent Glioblastomas

Stine Asferg Petterson, Mia Dahl Sørensen, Bjarne Winther Kristensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Glioblastomas (GBM) are highly infiltrative tumors and despite intensive treatment tumor recurrence is inevitable. The immune microenvironment in recurrent GBM is poorly characterized, but it is potentially influenced by therapeutic interventions with surgery, radiotherapy, and chemotherapy. The aim of this study was to obtain a deeper insight in the immune microenvironment in primary and recurrent GBM. Primary and recurrent glioblastoma samples from 18 patients were identified and expression profiling of 770 myeloid innate immune-related markers was performed. Leukemia inhibitory factor and pentraxin 3 were expressed at lower levels in recurrent tumors. Using in silico data and immunohistochemical staining, this was validated for pentraxin 3. Both high leukemia inhibitory factor and pentraxin 3 expression appeared to be associated with shorter survival in primary and recurrent GBM using in silico data. In primary GBM, gene set analysis also showed higher expression of genes involved in metabolism, extracellular matrix remodeling and complement activation, whereas genes involved in T cell activation and checkpoint signaling were expressed at higher levels in recurrent GBM. The reduced level of pentraxin 3 in recurrent glioblastomas and the gene set analysis results suggest an altered microenvironment in recurrent GBM that might be more active.

Original languageEnglish
JournalJournal of Neuropathology and Experimental Neurology
Volume79
Issue number9
Pages (from-to)975-985
Number of pages11
ISSN0022-3069
DOIs
Publication statusPublished - 1 Sept 2020

Keywords

  • Adult
  • Aged
  • Brain Neoplasms/immunology
  • C-Reactive Protein/analysis
  • Female
  • Gene Expression Profiling
  • Glioblastoma/immunology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local/immunology
  • Serum Amyloid P-Component/analysis
  • Transcriptome
  • Tumor Microenvironment/immunology

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