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An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma

2016; Cell Press; Volume: 29; Issue: 1 Linguagem: Inglês

10.1016/j.ccell.2015.12.004

1878-3686

A. Ari Hakimi, Ed Reznik, Chung‐Han Lee, Chad J. Creighton, A. Rose Brannon, Augustin Luna, Bülent Arman Aksoy, Eric Minwei Liu, Ronglai Shen, William Lee, Chen Yang, Steve Stirdivant, Paul Russo, Ying‐Bei Chen, Satish K. Tickoo, Victor E. Reuter, Emily H. Cheng, Chris Sander, James J. Hsieh,

Renal cell carcinoma treatment

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.