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Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival

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Listed:
  • Marie Duhamel

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Lauranne Drelich

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Maxence Wisztorski

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Soulaimane Aboulouard

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Jean-Pascal Gimeno

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Nina Ogrinc

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Patrick Devos

    (ULR 2694 - METRICS: Évaluation des technologies de santé et des pratiques médicales)

  • Tristan Cardon

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM))

  • Michael Weller

    (University Hospital and University of Zurich)

  • Fabienne Escande

    (CHU Lille)

  • Fahed Zairi

    (CHU Lille, Service de neurochirurgie)

  • Claude-Alain Maurage

    (CHU Lille)

  • Émilie Rhun

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM)
    University Hospital and University of Zurich
    CHU Lille)

  • Isabelle Fournier

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM)
    Institut Universitaire de France (IUF))

  • Michel Salzet

    (Réponse Inflammatoire et Spectrométrie de Masse (PRISM)
    Institut Universitaire de France (IUF))

Abstract

Molecular heterogeneity is a key feature of glioblastoma that impedes patient stratification and leads to large discrepancies in mean patient survival. Here, we analyze a cohort of 96 glioblastoma patients with survival ranging from a few months to over 4 years. 46 tumors are analyzed by mass spectrometry-based spatially-resolved proteomics guided by mass spectrometry imaging. Integration of protein expression and clinical information highlights three molecular groups associated with immune, neurogenesis, and tumorigenesis signatures with high intra-tumoral heterogeneity. Furthermore, a set of proteins originating from reference and alternative ORFs is found to be statistically significant based on patient survival times. Among these proteins, a 5-protein signature is associated with survival. The expression of these 5 proteins is validated by immunofluorescence on an additional cohort of 50 patients. Overall, our work characterizes distinct molecular regions within glioblastoma tissues based on protein expression, which may help guide glioblastoma prognosis and improve current glioblastoma classification.

Suggested Citation

  • Marie Duhamel & Lauranne Drelich & Maxence Wisztorski & Soulaimane Aboulouard & Jean-Pascal Gimeno & Nina Ogrinc & Patrick Devos & Tristan Cardon & Michael Weller & Fabienne Escande & Fahed Zairi & Cl, 2022. "Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34208-6
    DOI: 10.1038/s41467-022-34208-6
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    References listed on IDEAS

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    1. David Capper & David T. W. Jones & Martin Sill & Volker Hovestadt & Daniel Schrimpf & Dominik Sturm & Christian Koelsche & Felix Sahm & Lukas Chavez & David E. Reuss & Annekathrin Kratz & Annika K. We, 2018. "DNA methylation-based classification of central nervous system tumours," Nature, Nature, vol. 555(7697), pages 469-474, March.
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