Gene Expression Integration into Pathway Modules Reveals a Pan-Cancer Metabolic Landscape.

TitleGene Expression Integration into Pathway Modules Reveals a Pan-Cancer Metabolic Landscape.
Publication TypeJournal Article
Year of Publication2018
AuthorsCubuk, C, Hidalgo, MR, Amadoz, A, Pujana, MA, Mateo, F, Herranz, C, Carbonell-Caballero, J, Dopazo, J
JournalCancer Res
Volume78
Issue21
Pagination6059-6072
Date Published2018 11 01
ISSN1538-7445
KeywordsCell Line, Tumor; Cluster Analysis; Disease Progression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Kaplan-Meier Estimate; Metabolome; mutation; Neoplasms; Oncogenes; Phenotype; Prognosis; RNA, Small Interfering; Sequence Analysis, RNA; Transcriptome; Treatment Outcome
Abstract

Metabolic reprogramming plays an important role in cancer development and progression and is a well-established hallmark of cancer. Despite its inherent complexity, cellular metabolism can be decomposed into functional modules that represent fundamental metabolic processes. Here, we performed a pan-cancer study involving 9,428 samples from 25 cancer types to reveal metabolic modules whose individual or coordinated activity predict cancer type and outcome, in turn highlighting novel therapeutic opportunities. Integration of gene expression levels into metabolic modules suggests that the activity of specific modules differs between cancers and the corresponding tissues of origin. Some modules may cooperate, as indicated by the positive correlation of their activity across a range of tumors. The activity of many metabolic modules was significantly associated with prognosis at a stronger magnitude than any of their constituent genes. Thus, modules may be classified as tumor suppressors and oncomodules according to their potential impact on cancer progression. Using this modeling framework, we also propose novel potential therapeutic targets that constitute alternative ways of treating cancer by inhibiting their reprogrammed metabolism. Collectively, this study provides an extensive resource of predicted cancer metabolic profiles and dependencies. Combining gene expression with metabolic modules identifies molecular mechanisms of cancer undetected on an individual gene level and allows discovery of new potential therapeutic targets. .

DOI10.1158/0008-5472.CAN-17-2705
Alternate JournalCancer Res.
PubMed ID30135189