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

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 spectr...

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Autores principales: Duhamel, Marie, Drelich, Lauranne, Wisztorski, Maxence, Aboulouard, Soulaimane, Gimeno, Jean-Pascal, Ogrinc, Nina, Devos, Patrick, Cardon, Tristan, Weller, Michael, Escande, Fabienne, Zairi, Fahed, Maurage, Claude-Alain, Le Rhun, Émilie, Fournier, Isabelle, Salzet, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636229/
https://www.ncbi.nlm.nih.gov/pubmed/36333286
http://dx.doi.org/10.1038/s41467-022-34208-6
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author Duhamel, Marie
Drelich, Lauranne
Wisztorski, Maxence
Aboulouard, Soulaimane
Gimeno, Jean-Pascal
Ogrinc, Nina
Devos, Patrick
Cardon, Tristan
Weller, Michael
Escande, Fabienne
Zairi, Fahed
Maurage, Claude-Alain
Le Rhun, Émilie
Fournier, Isabelle
Salzet, Michel
author_facet Duhamel, Marie
Drelich, Lauranne
Wisztorski, Maxence
Aboulouard, Soulaimane
Gimeno, Jean-Pascal
Ogrinc, Nina
Devos, Patrick
Cardon, Tristan
Weller, Michael
Escande, Fabienne
Zairi, Fahed
Maurage, Claude-Alain
Le Rhun, Émilie
Fournier, Isabelle
Salzet, Michel
author_sort Duhamel, Marie
collection PubMed
description 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.
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spelling pubmed-96362292022-11-06 Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival Duhamel, Marie Drelich, Lauranne Wisztorski, Maxence Aboulouard, Soulaimane Gimeno, Jean-Pascal Ogrinc, Nina Devos, Patrick Cardon, Tristan Weller, Michael Escande, Fabienne Zairi, Fahed Maurage, Claude-Alain Le Rhun, Émilie Fournier, Isabelle Salzet, Michel Nat Commun Article 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. Nature Publishing Group UK 2022-11-04 /pmc/articles/PMC9636229/ /pubmed/36333286 http://dx.doi.org/10.1038/s41467-022-34208-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Duhamel, Marie
Drelich, Lauranne
Wisztorski, Maxence
Aboulouard, Soulaimane
Gimeno, Jean-Pascal
Ogrinc, Nina
Devos, Patrick
Cardon, Tristan
Weller, Michael
Escande, Fabienne
Zairi, Fahed
Maurage, Claude-Alain
Le Rhun, Émilie
Fournier, Isabelle
Salzet, Michel
Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title_full Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title_fullStr Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title_full_unstemmed Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title_short Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
title_sort spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636229/
https://www.ncbi.nlm.nih.gov/pubmed/36333286
http://dx.doi.org/10.1038/s41467-022-34208-6
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