An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma

Publication date: 11 January 2016
Source:Cancer Cell, Volume 29, Issue 1
Author(s): 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
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.

Graphical abstract

Teaser

Using metabolomic profiling, Ari Hakimi et al. show that clear cell renal cell carcinoma is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. They also develop metabolograms to allow integrating the TCGA transcriptomic data with their metabolomic data.


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