Title | A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Benedetti E, Liu EMinwei, Tang C, Kuo F, Buyukozkan M, Park T, Park J, Correa F, A Hakimi A, Intlekofer AM, Krumsiek J, Reznik E |
Journal | Nat Metab |
Volume | 5 |
Issue | 6 |
Pagination | 1029-1044 |
Date Published | 2023 Jun |
ISSN | 2522-5812 |
Keywords | Gene Expression Profiling, Humans, Metabolome, Metabolomics, Neoplasms, Transcriptome, Tumor Microenvironment |
Abstract | 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. |
DOI | 10.1038/s42255-023-00817-8 |
Alternate Journal | Nat Metab |
PubMed ID | 37337120 |
PubMed Central ID | PMC10290959 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States R03 CA252674 / CA / NCI NIH HHS / United States R37 CA276200 / CA / NCI NIH HHS / United States |