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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 11 2022
Historique:
received: 19 04 2022
accepted: 18 10 2022
pubmed: 6 11 2022
medline: 9 11 2022
entrez: 5 11 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36333286
doi: 10.1038/s41467-022-34208-6
pii: 10.1038/s41467-022-34208-6
pmc: PMC9636229
doi:

Substances chimiques

Proteome 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6665

Informations de copyright

© 2022. The Author(s).

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Auteurs

Marie Duhamel (M)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France. marie.duhamel@univ-lille.fr.

Lauranne Drelich (L)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Maxence Wisztorski (M)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Soulaimane Aboulouard (S)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Jean-Pascal Gimeno (JP)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Nina Ogrinc (N)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Patrick Devos (P)

Univ. Lille, CHU Lille, ULR 2694 - METRICS: Évaluation des technologies de santé et des pratiques médicales, F-59000, Lille, France.

Tristan Cardon (T)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France.

Michael Weller (M)

Department of Neurology & Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.

Fabienne Escande (F)

CHU Lille, Service de biochimie et biologie moléculaire, CHU Lille, F-59000, Lille, France.

Fahed Zairi (F)

CHU Lille, Service de neurochirurgie, F-59000, Lille, France.

Claude-Alain Maurage (CA)

CHU Lille, Service de biochimie et biologie moléculaire, CHU Lille, F-59000, Lille, France.

Émilie Le Rhun (É)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France. emilie.lerhun@usz.ch.
Department of Neurology & Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland. emilie.lerhun@usz.ch.
CHU Lille, Service de biochimie et biologie moléculaire, CHU Lille, F-59000, Lille, France. emilie.lerhun@usz.ch.

Isabelle Fournier (I)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France. isabelle.fournier@univ-lille.fr.
Institut Universitaire de France (IUF), 75000, Paris, France. isabelle.fournier@univ-lille.fr.

Michel Salzet (M)

Univ.Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), F-59000, Lille, France. michel.salzet@univ-lille.fr.
Institut Universitaire de France (IUF), 75000, Paris, France. michel.salzet@univ-lille.fr.

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