An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma

被引：591

作者：

Hakimi, A. Ari ^{[1
,2
]}

Reznik, Ed ^{[2
]}

Lee, Chung-Han ^{[3
,4
]}

Creighton, Chad J. ^{[5
]}

Brannon, A. Rose ^{[6
]}

Luna, Augustin ^{[2
]}

Aksoy, B. Arman ^{[2
]}

Liu, Eric Minwei ^{[2
]}

Shen, Ronglai ^{[7
]}

Lee, William ^{[8
]}

Chen, Yang ^{[9
]}

Stirdivant, Steve M. ^{[9
]}

Russo, Paul ^{[1
]}

Chen, Ying-Bei ^{[6
]}

Tickoo, Satish K. ^{[6
]}

Reuter, Victor E. ^{[6
]}

Cheng, Emily H. ^{[4
,6
]}

Sander, Chris ^{[2
]}

Hsieh, James J. ^{[3
,4
,10
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Computat Biol, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10065 USA

[4] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[5] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA

[9] Metabolon Inc, Durham, NC 27713 USA

[10] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

来源：

CANCER CELL | 2016年 / 29卷 / 01期

关键词：

HEPATOCELLULAR-CARCINOMA; CANCER-CELLS; GROWTH; HYPOXIA; CARBOXYLATION; BIOMARKERS; THERAPY; PATHWAY; PROTEIN; MODEL;

D O I：

10.1016/j.ccell.2015.12.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：104 / 116

页数：13

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