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Sci Rep. 2015 Jun 4;5:10738. doi: 10.1038/srep10738.

Flux balance analysis predicts essential genes in clear cell renal cell carcinoma metabolism.

Author information

1
Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg 41296, Sweden.
2
Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, United Kingdom.
3
1] Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, London WC2A 3LY, United Kingdom [2] Theodor-Boveri-Institute, Biocenter, Am Hubland, 97074 Würzburg, Germany [3] Comprehensive Cancer Center Mainfranken, Josef-Schneider-Str.6, 97080 Würzburg, Germany.

Abstract

Flux balance analysis is the only modelling approach that is capable of producing genome-wide predictions of gene essentiality that may aid to unveil metabolic liabilities in cancer. Nevertheless, a systemic validation of gene essentiality predictions by flux balance analysis is currently missing. Here, we critically evaluated the accuracy of flux balance analysis in two cancer types, clear cell renal cell carcinoma (ccRCC) and prostate adenocarcinoma, by comparison with large-scale experiments of gene essentiality in vitro. We found that in ccRCC, but not in prostate adenocarcinoma, flux balance analysis could predict essential metabolic genes beyond random expectation. Five of the identified metabolic genes, AGPAT6, GALT, GCLC, GSS, and RRM2B, were predicted to be dispensable in normal cell metabolism. Hence, targeting these genes may selectively prevent ccRCC growth. Based on our analysis, we discuss the benefits and limitations of flux balance analysis for gene essentiality predictions in cancer metabolism, and its use for exposing metabolic liabilities in ccRCC, whose emergent metabolic network enforces outstanding anabolic requirements for cellular proliferation.

PMID:
26040780
PMCID:
PMC4603759
DOI:
10.1038/srep10738
[Indexed for MEDLINE]
Free PMC Article

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