An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

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.

• Authors: A Ari Hakimi, Ed Reznik, Chung-Han Lee, Chad J Creighton, A Rose Brannon, Augustin Luna, B Arman Aksoy, Eric Minwei Liu, Ronglai Shen, William Lee, Yang Chen, Steve M Stirdivant, Paul Russo, Ying Bei Chen, Satish K Tickoo, Victor E Reuter, Emily H Cheng, Chris Sander, James J Hsieh
• Journal: Cancer cell (Cancer Cell) Vol. 29 Issue 1 Pg. 104-116 (Jan 11 2016) ISSN: 1878-3686 [Electronic] United States
• PMID: 26766592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Renal Cell (diagnosis, genetics)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Kidney Neoplasms (diagnosis, genetics)
• Metabolomics (methods)
• Neoplasm Staging
• Prognosis