TY  - JOUR
AU  - Cosenza-Contreras, Miguel
AU  - Schäfer, Agnes
AU  - Sing, Justin
AU  - Cook, Lena
AU  - Stillger, Maren N
AU  - Chen, Chia-Yi
AU  - Hidalgo, Jose Villacorta
AU  - Pinter, Niko
AU  - Meyer, Larissa
AU  - Werner, Tilman
AU  - Bug, Darleen
AU  - Haberl, Zeno
AU  - Kübeck, Oliver
AU  - Zhao, Kai
AU  - Stei, Susanne
AU  - Gafencu, Anca Violeta
AU  - Ionita, Radu
AU  - Brehar, Felix M
AU  - Ferrer-Lozano, Jaime
AU  - Ribas, Gloria
AU  - Cerdá-Alberich, Leo
AU  - Martí-Bonmatí, Luis
AU  - Nimsky, Christopher
AU  - Van Straaten, Alexis
AU  - Biniossek, Martin L
AU  - Föll, Melanie
AU  - Cabezas-Wallscheid, Nina
AU  - Büscher, Jörg
AU  - Röst, Hannes
AU  - Arnoux, Armelle
AU  - Bartsch, Jörg W
AU  - Schilling, Oliver
TI  - Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism.
JO  - Neuro-Oncology
VL  - 26
IS  - 3
SN  - 1522-8517
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2023-02181
SP  - 488-502
PY  - 2024
N1  - 2024 Mar 4;26(3):488-502
AB  - 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.
KW  - acid ceramidase (ASAH1) (Other)
KW  - glioblastoma (Other)
KW  - lipidomics (Other)
KW  - proteomics (Other)
KW  - tumor microenvironment (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37882631
DO  - DOI:10.1093/neuonc/noad208
UR  - https://inrepo02.dkfz.de/record/285008
ER  -