Apr 26, 2016

Pan-cancer analysis of the metabolic reaction network

BioRxiv : the Preprint Server for Biology
Francesco Gatto, Jens Nielsen

Abstract

Metabolic reprogramming is considered a hallmark of malignant transformation. However, it is not clear whether the network of metabolic reactions expressed by cancers of different origin differ from each other nor from normal human tissues. In this study, we reconstructed functional and connected genome-scale metabolic models for 917 primary tumors based on the probability of expression for 3,765 reference metabolic genes in the sample. This network-centric approach revealed that tumor metabolic networks are largely similar in terms of accounted reactions, despite diversity in the expression of the associated genes. On average, each network contained 4,721 reactions, of which 74% were core reactions (present in >95% of all models). Whilst 99.3% of the core reactions were classified as housekeeping also in normal tissues, we identified reactions catalyzed by ARG2, RHAG, SLC6 and SLC16 family gene members, and PTGS1 and PTGS2 as core exclusively in cancer. The remaining 26% of the reactions were contextual reactions. Their inclusion was dependent in one case (GLS2) on the absence of TP53 mutations and in 94.6% of cases on differences in cancer types. This dependency largely resembled differences in expression patterns in the corr...Continue Reading

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Mentioned in this Paper

TP53 gene
Metabolic Process, Cellular
Study
Cyclooxygenase 2
Patterns
Genes
Metabolic Networks
Primary Neoplasm
Female Reproductive System
ARG2

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