An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.
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DOI：
10.1016/j.ccell.2015.12.004
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发表时间：
2016-01-11
期刊：
影响因子：
50.3
通讯作者：
Hsieh JJ
中科院分区：
文献类型：
--
作者：
Hakimi AA;Reznik E;Lee CH;Creighton CJ;Brannon AR;Luna A;Aksoy BA;Liu EM;Shen R;Lee W;Chen Y;Stirdivant SM;Russo P;Chen YB;Tickoo SK;Reuter VE;Cheng EH;Sander C;Hsieh JJ
代谢失调是癌症的一个标志，表现为代谢物的改变。我们对138对匹配的透明细胞肾细胞癌(ccRCC)/正常组织对进行了代谢组学分析，发现ccRCC的特征是中心碳代谢、单碳代谢和抗氧化反应的广泛变化。肿瘤进展和转移与谷胱甘肽和半胱氨酸/蛋氨酸代谢途径的代谢物增加有关。我们开发了一个分析管道和可视化工具（“代谢图”），以弥合TCGA转录组分析和我们的代谢组数据之间的差距，这使我们能够组装一个集成的途径水平的代谢图谱，并证明转录组和代谢组之间的不一致。最后，对高谷胱甘肽群进行表达谱分析，这对应于ccRCC TCGA队列中的低生存亚组。
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 anti-oxidant 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 correspond to a poor-survival subgroup in the ccRCC TCGA cohort.