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@ARTICLE{CosenzaContreras:285008,
author = {M. Cosenza-Contreras and A. Schäfer and J. Sing and L.
Cook and M. N. Stillger and C.-Y. Chen and J. V. Hidalgo and
N. Pinter and L. Meyer and T. Werner and D. Bug and Z.
Haberl and O. Kübeck and K. Zhao and S. Stei and A. V.
Gafencu and R. Ionita and F. M. Brehar and J. Ferrer-Lozano
and G. Ribas and L. Cerdá-Alberich and L. Martí-Bonmatí
and C. Nimsky and A. Van Straaten and M. L. Biniossek and M.
Föll$^*$ and N. Cabezas-Wallscheid and J. Büscher and H.
Röst and A. Arnoux and J. W. Bartsch and O. Schilling},
title = {{P}roteometabolomics of initial and recurrent glioblastoma
highlights an increased immune cell signature with altered
lipid metabolism.},
journal = {Neuro-Oncology},
volume = {26},
number = {3},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2023-02181},
pages = {488-502},
year = {2024},
note = {2024 Mar 4;26(3):488-502},
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.},
keywords = {acid ceramidase (ASAH1) (Other) / glioblastoma (Other) /
lipidomics (Other) / proteomics (Other) / tumor
microenvironment (Other)},
cin = {FR01},
ddc = {610},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37882631},
doi = {10.1093/neuonc/noad208},
url = {https://inrepo02.dkfz.de/record/285008},
}