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

Autor:	Cosenza-Contreras M; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Schäfer A; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Sing J; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Cook L; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Stillger MN; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany., Chen CY; Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany., Villacorta Hidalgo J; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany., Pinter N; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany., Meyer L; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany., Werner T; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany., Bug D; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Haberl Z; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Kübeck O; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Zhao K; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Stei S; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Gafencu AV; Institute of Cellular Biology and Pathology ' Nicolae Simionescu,' Bucharest, Romania., Ionita R; Institute of Cellular Biology and Pathology ' Nicolae Simionescu,' Bucharest, Romania., Brehar FM; Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.; Bagdasar-Arseni' Emergency Clinical Hospital, Bucharest, Romania., Ferrer-Lozano J; Department of Pathology Hospital Universitari i Politècnic La Fe, València, Spain., Ribas G; Biomedical Imaging Research Group (GIBI230) Instituto de Investigación Sanitaria La Fe, Valencia, Spain., Cerdá-Alberich L; Biomedical Imaging Research Group (GIBI230) Instituto de Investigación Sanitaria La Fe, Valencia, Spain., Martí-Bonmatí L; Department of Pathology Hospital Universitari i Politècnic La Fe, València, Spain.; Department of Radiology Hospital Universitari i Politècnic La Fe, València, Spain., Nimsky C; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Van Straaten A; Department of medical informatics and evaluation of practices, Assistance Publique-Hôpitaux de Paris Centre, Paris University & European Hospital Georges Pompidou, Paris, France., Biniossek ML; Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany., Föll M; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Khoury College of Computer Sciences, Northeastern University, Boston, USA., Cabezas-Wallscheid N; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Büscher J; Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Röst H; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada., Arnoux A; Clinical Epidemiology INSERM & Clinical Research Unit, Assistance Publique-Hôpitaux de Paris Centre, Paris University & European Hospital Georges Pompidou, Paris, France., Bartsch JW; Department of Neurosurgery, Philipps University Marburg, Marburg, Germany., Schilling O; Institute of Surgical Pathology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2024 Mar 04; Vol. 26 (3), pp. 488-502.
DOI:	10.1093/neuonc/noad208
Abstrakt:	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 coculture 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. (© 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.)
Databáze:	MEDLINE
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