An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma

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. [Display omitted] •ccRCC exhibit dysregulated oxidative phosphorylation and amino acid metabolism•Clinical progression of ccRCC manifested with elevated glutathione and dipeptides•Metabolomic clustering of human ccRCC identified distinct high- and low-risk subsets•Metabolograms visualize metabolomic, transcriptomic, and clinical data of ccRCC 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.