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组织代谢组学分析揭示结直肠癌中的主要代谢改变。

Tissue metabolic profiling reveals major metabolic alteration in colorectal cancer.

机构信息

The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Mol Omics. 2021 Jun 14;17(3):464-471. doi: 10.1039/d1mo00022e.

Abstract

Metabolic reprogramming is a hallmark of cancer, which is still far from being fully understood in colorectal cancer. In order to characterize the metabolic changes in colorectal cancer, we performed metabolomics analysis of paired colon tissues from colorectal cancer patients by using a liquid chromatography-mass spectrometry (LC-MS)-based method. Bioinformation analysis was used to define important metabolites and metabolic pathways, as well as the prognosis significance and expression levels of the key molecules. The results indicated that the metabolite phenotype in cancerous colon tissues was obviously different from their normal counterpart, and we identified a series of important metabolic changes in colorectal cancer, including decreased trends of glucose, citrate, serotonin, 5-hydroxytryptophol and 5-hydroxyindoleacetate, as well as increased trends of glutamate, glutathione, creatine, proline, lactate, fructose 1,6-bisphosphate, succinate, tryptophan, kynurenine and long chain acyl-carnitines. These metabolites are mainly implicated in energy metabolism, amino acid metabolism, glutathione metabolism and fatty acid metabolism. In addition, we found that the expression levels of several key molecules in these pathways were closely correlated with the prognosis of colorectal cancer patients. This study characterizes the metabolic profile in colorectal cancer tissues and provides more insightful understanding of the metabolic reprogramming of colorectal cancer.

摘要

代谢重编程是癌症的一个标志,这在结直肠癌中仍远未被充分理解。为了描述结直肠癌中的代谢变化,我们使用基于液相色谱-质谱(LC-MS)的方法对结直肠癌患者的配对结肠组织进行了代谢组学分析。生物信息学分析用于定义重要的代谢物和代谢途径,以及关键分子的预后意义和表达水平。结果表明,癌组织中的代谢表型明显不同于其正常对应物,我们确定了一系列结直肠癌中的重要代谢变化,包括葡萄糖、柠檬酸、血清素、5-羟色醇和 5-羟吲哚乙酸的下降趋势,以及谷氨酸、谷胱甘肽、肌酸、脯氨酸、乳酸、果糖 1,6-二磷酸、琥珀酸、色氨酸、犬尿氨酸和长链酰基肉碱的上升趋势。这些代谢物主要涉及能量代谢、氨基酸代谢、谷胱甘肽代谢和脂肪酸代谢。此外,我们发现这些途径中的几个关键分子的表达水平与结直肠癌患者的预后密切相关。本研究描述了结直肠癌组织中的代谢特征,为结直肠癌的代谢重编程提供了更深入的理解。

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