A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
22
11
2022
accepted:
09
05
2023
medline:
27
6
2023
pubmed:
20
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
Tumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments.
Identifiants
pubmed: 37337120
doi: 10.1038/s42255-023-00817-8
pii: 10.1038/s42255-023-00817-8
pmc: PMC10290959
doi:
Types de publication
Meta-Analysis
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1029-1044Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA252674
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA251543
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA276200
Pays : United States
Informations de copyright
© 2023. The Author(s).
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