The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism
The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism
复制标题
DOI：
10.1158/0008-5472.can-12-1572-t
复制
发表时间：
2012-11-15
期刊：
影响因子：
11.2
通讯作者：
Gillies, Robert
中科院分区：
文献类型：
--
作者：
Chinnaiyan, Prakash;Kensicki, Elizabeth;Gillies, Robert
虽然通过大规模的基因和蛋白质表达分析在理解胶质母细胞瘤生物学方面已经取得了相当大的进展，但对促进其侵袭性表型的潜在代谢变化知之甚少。我们对患者来源的胶质瘤标本进行了全球代谢组学分析，并确定了区分低级别和高级别肿瘤的特定代谢程序，胶质母细胞瘤的代谢特征反映了合成代谢的加速。当结合转录谱时，我们鉴定了间充质亚型的代谢表型包括糖酵解中间产物磷酸烯醇式丙酮酸的积累和丙酮酸激酶活性的降低。代谢谱无偏见的等级聚类确定了三个亚类，我们称之为能量分解代谢、合成代谢和磷脂分解代谢与预后相关。这些研究代表了胶质瘤的第一个全球代谢组图谱，提供了一个先前未描述的了解其代谢异质性的窗口，并为设计针对这种快速致命的恶性肿瘤的新陈代谢的策略提供了必要的框架。癌症资源；72(22)；5878-88。(C)2012年AACR。
Although considerable progress has been made toward understanding glioblastoma biology through large-scale genetic and protein expression analyses, little is known about the underlying metabolic alterations promoting their aggressive phenotype. We conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low-and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, we identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which we term energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy. Cancer Res; 72(22); 5878-88. (C) 2012 AACR.