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  Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism

Cosenza-Contreras, M., Schäfer, A., Sing, J., Cook, L., Stillger, M. N., Chen, C.-Y., et al. (2023). Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism. Neuro-Oncology: official journal of the World Federation of Neuro-Oncology, noad208. doi:10.1093/neuonc/noad208.

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The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
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 Creators:
Cosenza-Contreras, Miguel1, Author
Schäfer, Agnes1, Author
Sing, Justin1, Author
Cook, Lena1, Author
Stillger, Maren N1, Author
Chen, Chia-Yi1, Author
Hidalgo, Jose Villacorta1, Author
Pinter, Niko1, Author
Meyer, Larissa1, Author
Werner, Tilman1, Author
Bug, Darleen1, Author
Haberl, Zeno1, Author
Kübeck, Oliver1, Author
Zhao, Kai1, Author
Stei, Susanne1, Author
Gafencu, Anca Violeta1, Author
Ionita, Radu1, Author
Brehar, Felix M1, Author
Ferrer-Lozano, Jaime1, Author
Ribas, Gloria1, Author
Cerdá-Alberich, Leo1, AuthorMartí-Bonmatí, Luis1, AuthorNimsky, Christopher1, AuthorStraaten, Alexis Van1, AuthorBiniossek, Martin L1, AuthorFöll, Melanie1, AuthorCabezas-Wallscheid, Nina2, Author           Büscher, Jörg Martin3, Author           Röst, Hannes1, AuthorArnoux, Armelle1, AuthorBartsch, Jörg W1, AuthorSchilling, Oliver1, Author more..
Affiliations:
1External Organizations, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
3Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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Free keywords: acid ceramidase (ASAH1); glioblastoma; lipidomics; proteomics; tumor microenvironment.
 Abstract: Background: There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment.

Methods: We assembled a cohort of patient-matched initial (iGBM) and recurrent (rGBM) specimens of resected GBM. Proteome and metabolome composition were determined by mass spectrometry-based techniques. We performed neutrophil-GBM cell co-culture experiments to evaluate the behavior of rGBM-enriched proteins in the tumor microenvironment. ELISA-based quantitation of candidate proteins was performed to test the association of their plasma concentrations in iGBM with the onset of recurrence.

Results: Proteomic profiles reflect increased immune cell infiltration and extracellular matrix reorganization in rGBM. ASAH1, SYMN, and GPNMB were highly enriched proteins in rGBM. Lipidomics indicates the downregulation of ceramides in rGBM. Cell analyses suggest a role for ASAH1 in neutrophils and its localization in extracellular traps. Plasma concentrations of ASAH1 and SYNM show an association with time-to-recurrence.

Conclusions: We describe the potential importance of ASAH1 in tumor progression and development of rGBM via metabolic rearrangement and showcase the feedback from the tumor microenvironment to plasma proteome profiles. We report the potential of ASAH1 and SYNM as plasma markers of rGBM progression. The published datasets can be considered as a resource for further functional and biomarker studies involving additional -omics technologies.

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Language(s): eng - English
 Dates: 2023-10-26
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1093/neuonc/noad208
 Degree: -

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Title: Neuro-Oncology : official journal of the World Federation of Neuro-Oncology
  Other : Neuro-Oncology
  Abbreviation : Neuro Oncol
Source Genre: Journal
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Publ. Info: USA : Oxford : Oxford Univ. Press
Pages: - Volume / Issue: - Sequence Number: noad208 Start / End Page: - Identifier: ISSN: 1523-5866
CoNE: https://pure.mpg.de/cone/journals/resource/1523-5866