A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer.
A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer.
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DOI：
10.1038/srep29662
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发表时间：
2016-07-13
影响因子：
4.6
通讯作者：
Ruppin E
中科院分区：
文献类型：
--
作者：
Auslander N;Yizhak K;Weinstock A;Budhu A;Tang W;Wang XW;Ambs S;Ruppin E
细胞过程调节中断被认为是癌症的标志之一。我们分析了从乳腺癌和肝细胞癌患者中共同收集的代谢组学和转录组学资料，以探讨代谢酶的表达与参与其催化反应的代谢物水平之间的关联。令人惊讶的是，与非癌性相邻组织相比，乳腺癌和肝细胞肿瘤的基因-代谢物相关性都有所增加。接下来，我们从催化代谢物的酶基因的表达中建立了代谢物水平的预测因子。将这些预测因子应用于大量乳腺癌样本，我们发现，关键癌症相关代谢物（包括葡萄糖、甘氨酸、丝氨酸和乙酸盐）的耗竭水平与患者生存率的改善显著相关。因此，我们表明，乳腺癌中各种代谢物的水平可以从转录组中成功预测，超出了有限的测量值。
Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.