title: 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.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.forename: Ed
authors.initials: E
authors.lastname: Reznik
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: A Rose
authors.initials: AR
authors.lastname: Brannon
authors.forename: Augustin
authors.initials: A
authors.lastname: Luna
authors.forename: B Arman
authors.initials: BA
authors.lastname: Aksoy
authors.forename: Eric Minwei
authors.initials: EM
authors.lastname: Liu
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: William
authors.initials: W
authors.lastname: Lee
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Steve M
authors.initials: SM
authors.lastname: Stirdivant
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Ying Bei
authors.initials: YB
authors.lastname: Chen
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Emily H
authors.initials: EH
authors.lastname: Cheng
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D055432:Metabolomics / Q000379:methods; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor