An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

TitleAn Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.
Publication TypeJournal Article
Year of Publication2016
AuthorsA Hakimi, A, Reznik, E, Lee, C-H, Creighton, CJ, A Brannon, R, Luna, A, B Aksoy, A, Liu, EMinwei, Shen, R, Lee, W, Chen, Y, Stirdivant, SM, Russo, P, Chen, YBei, Tickoo, SK, Reuter, VE, Cheng, EH, Sander, C, Hsieh, JJ
JournalCancer Cell
Volume29
Issue1
Pagination104-116
Date Published2016 Jan 11
ISSN1878-3686
KeywordsBiomarkers, Tumor, Carcinoma, Renal Cell, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Humans, Kidney Neoplasms, Metabolomics, Neoplasm Staging, Prognosis
Abstract

Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort.

DOI10.1016/j.ccell.2015.12.004
Alternate JournalCancer Cell
PubMed ID26766592
PubMed Central IDPMC4809063
Grant ListT32 CA160001 / CA / NCI NIH HHS / United States
5U24CA143843 / CA / NCI NIH HHS / United States
R01 CA138505 / CA / NCI NIH HHS / United States
P30CA125123 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
5T32CA160001 / CA / NCI NIH HHS / United States

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