Tissue metabolomics of hepatocellular carcinoma: tumor energy metabolism and the role of transcriptomic classification.
Tissue metabolomics of hepatocellular carcinoma: tumor energy metabolism and the role of transcriptomic classification.
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DOI：
10.1002/hep.26350
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发表时间：
2013-07
期刊：
影响因子：
13.5
通讯作者：
Idle, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Beyoglu, Diren;Imbeaud, Sandrine;Maurhofer, Olivier;Bioulac-Sage, Paulette;Zucman-Rossi, Jessica;Dufour, Jean-Francois;Idle, Jeffrey R.
肝细胞癌（HCC）是癌症死亡的最常见原因之一。大量的HCC代谢组学研究已经在生物流体中产生了上调和下调的分子，但是关于用于HCC早期检测的可利用的生物标志物还没有出现真实的共识。我们在这里报告了一种不同的方法，一个联合转录组学和代谢组学研究肝癌的能量代谢。采用基于代谢组学的气相色谱-质谱（GCMS）研究了来自相同患者的31对HCC肿瘤和相应的非肿瘤肝组织。HCC的特征在于葡萄糖、甘油3-和2-磷酸、苹果酸、丙氨酸、肌醇和亚油酸的大约2倍消耗。数据与涉及糖酵解比线粒体氧化磷酸化增加四倍的代谢重塑一致。第二组59例经转录组学分型并分为G1至G6亚组的HCC也进行了GCMS组织代谢组学研究。在葡萄糖、乳酸、丙氨酸、甘油3-磷酸、苹果酸、肌醇或硬脂酸组织浓度中没有发现差异，表明在亚组G5和G6中由CTNNB 1突变激活的Wnt/β-连环蛋白途径没有表现出特异性代谢重塑。然而，亚组G1的1-硬脂酰甘油、1-棕榈酰甘油和棕榈酸的组织浓度显著降低，表明G1的高血清甲胎蛋白表型（与已知的脂质分解代谢酶过度表达相关）可通过代谢组学检测为脂质分解酶增加。组织代谢组学提供了关于HCC肿瘤代谢重塑的精确生化信息，从线粒体氧化到有氧糖酵解，以及分子亚型对这一过程的影响。
Hepatocellular carcinoma (HCC) is one of the commonest causes of death from cancer. A plethora of metabolomic investigations of HCC have yielded molecules in biofluids that are both up- and downregulated but no real consensus has emerged regarding exploitable biomarkers for early detection of HCC. We report here a different approach, a combined transcriptomics and metabolomics study of energy metabolism in HCC. A panel of 31 pairs of HCC tumors and corresponding non-tumor liver tissues from the same patients was investigated by gas chromatography-mass spectrometry (GCMS) based metabolomics. HCC was characterized by approximately two-fold depletion of glucose, glycerol 3- and 2-phosphate, malate, alanine, myo-inositol, and linoleic acid. Data are consistent with a metabolic remodeling involving a four-fold increase in glycolysis over mitochondrial oxidative phosphorylation. A second panel of 59 HCC that had been typed by transcriptomics and classified in G1 to G6 subgroups was also subjected to GCMS tissue metabolomics. No differences in glucose, lactate, alanine, glycerol 3-phosphate, malate, myo-inositol or stearic acid tissue concentrations were found, suggesting that the Wnt/β-catenin pathway activated by CTNNB1 mutation in subgroups G5 and G6 did not exhibit specific metabolic remodeling. However, subgroup G1 had markedly reduced tissue concentrations of 1-stearoylglycerol, 1-palmitoylglycerol, and palmitic acid, suggesting that the high serum α-fetoprotein phenotype of G1, associated with the known overexpression of lipid catabolic enzymes, could be detected through metabolomics as increased lipid catabolism. Tissue metabolomics yielded precise biochemical information regarding HCC tumor metabolic remodeling from mitochondrial oxidation to aerobic glycolysis and the impact of molecular subtypes on this process.
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影响因子：
29.4
作者：
Laurent-Puig, P;Legoix, P;Zucman-Rossi, J
通讯作者：
Zucman-Rossi, J
影响因子：
4.5
作者：
Lencioni, Riccardo
通讯作者：
Lencioni, Riccardo
影响因子：
3.4
作者：
Chafey, Philippe;Finzi, Laetitia;Perret, Christine
通讯作者：
Perret, Christine
影响因子：
3.4
作者：
Lanz C;Patterson AD;Slavík J;Krausz KW;Ledermann M;Gonzalez FJ;Idle JR
通讯作者：
Idle JR
影响因子：
45.3
作者：
Altekruse, Sean F.;McGlynn, Katherine A.;Reichman, Marsha E.
通讯作者：
Reichman, Marsha E.