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

Marie Duhamel (), Lauranne Drelich, Maxence Wisztorski, Soulaimane Aboulouard, Jean-Pascal Gimeno, Nina Ogrinc, Patrick Devos, Tristan Cardon, Michael Weller, Fabienne Escande, Fahed Zairi, Claude-Alain Maurage, Émilie Rhun (), Isabelle Fournier () and Michel Salzet ()
Additional contact information
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)
Isabelle Fournier: Réponse Inflammatoire et Spectrométrie de Masse (PRISM)
Michel Salzet: Réponse Inflammatoire et Spectrométrie de Masse (PRISM)

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34208-6

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