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使用高分辨率魔角旋转1H核磁共振波谱结合多变量数据分析对人类肝细胞癌进行代谢组学研究。

Metabonomic studies of human hepatocellular carcinoma using high-resolution magic-angle spinning 1H NMR spectroscopy in conjunction with multivariate data analysis.

作者信息

Yang Yongxia, Li Chenglong, Nie Xiu, Feng Xiansong, Chen Wenxue, Yue Yong, Tang Huiru, Deng Feng

机构信息

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan 430071, P. R. China.

出版信息

J Proteome Res. 2007 Jul;6(7):2605-14. doi: 10.1021/pr070063h. Epub 2007 Jun 12.

DOI:10.1021/pr070063h
PMID:17564425
Abstract

High-resolution magic-angle spinning (MAS) 1H nuclear magnetic resonance spectroscopy has been employed to characterize the metabolite composition (i.e., metabonome) of the human hepatocellular carcinoma (HCC) tumor in combination with principal component analysis (PCA). The results showed that (a) the metabonomes of both low-grade HCC and high-grade HCC tumors differ markedly from that of the adjacent non-involved tissues; and (b) low-grade HCC tumors have clear differences in metabonome from that of the high-grade HCC tumors. Compared with the non-involved adjacent liver tissues, HCC tumors had elevated levels of lactate, glutamate, glutamine, glycine, leucine, alanine, choline metabolites, and phosphorylethanolamine (PE), but declined levels of triglycerides, glucose, and glycogen. The levels of lactate, amino acids including glutamate, glutamine, glycine, leucine and alanine, choline and phosphorylethanolamine (PE) were higher but the levels of PC, GPC, triglycerides, glucose, and glycogen were lower in high-grade HCC than in low-grade HCC tumors. Compared with non-cirrhotic, low-grade HCC tumors, the cirrhotic, low-grade HCC tumors showed statistically significant increases in lactate, phosphocholine (PC), and glycerophosphocholine (GPC). The necrosis in HCC tumors resulted in a drastic increase in the levels of observable triglycerides, signals of which dominated their 1H NMR spectra. These results indicated that HRMAS combined with PCA offers a useful tool for understanding the tumor biochemistry and classification of liver tumor tissues; such tool may also have some potential for liver tumor diagnosis and prognosis even when some other disease processes are present.

摘要

高分辨率魔角旋转(MAS)1H核磁共振波谱已被用于结合主成分分析(PCA)来表征人类肝细胞癌(HCC)肿瘤的代谢物组成(即代谢组)。结果表明:(a)低级别HCC和高级别HCC肿瘤的代谢组均与相邻未受累组织的代谢组有显著差异;(b)低级别HCC肿瘤的代谢组与高级别HCC肿瘤的代谢组有明显差异。与未受累的相邻肝组织相比,HCC肿瘤中乳酸、谷氨酸、谷氨酰胺、甘氨酸、亮氨酸、丙氨酸、胆碱代谢物和磷酸乙醇胺(PE)水平升高,但甘油三酯、葡萄糖和糖原水平下降。高级别HCC中乳酸、包括谷氨酸、谷氨酰胺、甘氨酸、亮氨酸和丙氨酸在内的氨基酸、胆碱和磷酸乙醇胺(PE)的水平较高,但磷脂酰胆碱(PC)、甘油磷酸胆碱(GPC)、甘油三酯、葡萄糖和糖原的水平低于低级别HCC肿瘤。与非肝硬化的低级别HCC肿瘤相比,肝硬化的低级别HCC肿瘤中乳酸、磷酸胆碱(PC)和甘油磷酸胆碱(GPC)有统计学意义的升高。HCC肿瘤中的坏死导致可观察到的甘油三酯水平急剧增加,其信号在1H NMR光谱中占主导地位。这些结果表明,HRMAS结合PCA为理解肿瘤生物化学和肝肿瘤组织分类提供了一种有用的工具;即使存在一些其他疾病过程,这种工具在肝肿瘤诊断和预后方面也可能具有一定潜力。

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