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A pan-cancer metabolic atlas of the tumor microenvironment

Neha Rohatgi, Umesh Ghoshdastider, Probhonjon Baruah, Anders Jacobsen Skanderup
doi: https://doi.org/10.1101/2020.10.16.342519
Neha Rohatgi
1Genome Institute of Singapore, Agency for Science Technology and Research, Singapore
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Umesh Ghoshdastider
1Genome Institute of Singapore, Agency for Science Technology and Research, Singapore
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Probhonjon Baruah
1Genome Institute of Singapore, Agency for Science Technology and Research, Singapore
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Anders Jacobsen Skanderup
1Genome Institute of Singapore, Agency for Science Technology and Research, Singapore
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  • For correspondence: skanderupamj@gis.a-star.edu.sg
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Abstract

Tumors are heterogeneous cellular environments with entwined metabolic dependencies. Here, we used a tumor transcriptome deconvolution approach to profile the metabolic states of cancer and non-cancer (stromal) cells in bulk tumors of 20 solid tumor types. We identified metabolic genes and processes recurrently altered in cancer cells across tumor types, including pan-cancer upregulation of deoxythymidine triphosphate (dTTP) production. In contrast, the tryptophan catabolism rate limiting enzymes, IDO1 and TDO2, were highly overexpressed in stroma, suggesting that kynurenine-mediated suppression of antitumor immunity is predominantly constrained by the stroma. Oxidative phosphorylation was unexpectedly the most upregulated metabolic process in cancer cells compared to both stromal cells and a large atlas of cancer cell lines, suggesting that the Warburg effect may be less pronounced in cancer cells in vivo. Overall, our analysis highlights fundamental differences in metabolic states of cancer and stromal cells inside tumors and establishes a pan-cancer resource to interrogate tumor metabolism.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 16, 2020.
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A pan-cancer metabolic atlas of the tumor microenvironment
Neha Rohatgi, Umesh Ghoshdastider, Probhonjon Baruah, Anders Jacobsen Skanderup
bioRxiv 2020.10.16.342519; doi: https://doi.org/10.1101/2020.10.16.342519
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A pan-cancer metabolic atlas of the tumor microenvironment
Neha Rohatgi, Umesh Ghoshdastider, Probhonjon Baruah, Anders Jacobsen Skanderup
bioRxiv 2020.10.16.342519; doi: https://doi.org/10.1101/2020.10.16.342519

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