Journal Article

DKFZ-2023-02181

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. ; Hidalgo, J. V. ; Pinter, N. ; Meyer, L. ; Werner, T. ; Bug, D. ; Haberl, Z. ; Kübeck, O. ; Zhao, K. ; Stei, S. ; Gafencu, A. V. ; Ionita, R. ; Brehar, F. M. ; Ferrer-Lozano, J. ; Ribas, G. ; Cerdá-Alberich, L. ; Martí-Bonmatí, L. ; Nimsky, C. ; Van Straaten, A. ; Biniossek, M. L. ; Föll, M.DKFZ* ; Cabezas-Wallscheid, N. ; Büscher, J. ; Röst, H. ; Arnoux, A. ; Bartsch, J. W. ; Schilling, O.

2024
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noad208

Abstract: 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.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.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.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.

Keyword(s): acid ceramidase (ASAH1) ; glioblastoma ; lipidomics ; proteomics ; tumor microenvironment

Note: 2024 Mar 4;26(3):488-502

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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