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中科院在研究肝癌组织非靶标代谢获得新发现

文字:[大][中][小] 发布时间:2013-11-15  浏览次数:4333

  近日,中科院利用液相色谱—质谱技术探索肝癌组织非靶标代谢获得新发现。这项研究是由大连化学物理研究所研究员许国旺团队与上海东方肝胆医院王红阳院士课题组共同完成。相关文章发表于《Cancer Research 》杂志上。

中科院在研究肝癌组织非靶标代谢获得新发现
  中科院在研究肝癌组织非靶标代谢获得新发现

  肝癌在临床上早诊困难,治疗预后效果差。深入了解肝癌的发病机理对制定治疗方案、改善治疗效果、降低肝癌发病率和死亡率都有重要的意义。组织代谢组学方法是研究肝癌代谢异常的有力工具,可为肝癌发病机理的阐明和新型诊断标志物的发现提供依据。

  研究人员基于超高效液相色谱—高分辨质谱分析平台,对50例肝癌患者的癌组织、癌旁近端组织和远端组织进行了非靶标代谢谱分析,结合多变量数据处理方法和生物信息学技术,从整体层面阐明了肝癌微环境的代谢紊乱状况。

  结果表明,肝癌患者出现了大量的代谢异常,主要包括糖酵解加速、三羧酸循环抑制、糖异生和β-氧化加快以进一步提供能量、脂肪酸代谢相关的Δ-12脱氢酶活性显着下调。此外,谷胱甘肽等抗氧化分子水平增高,炎症相关的多不饱和脂肪酸和磷脂酶A2水平下降。

  研究人员将组织中发现的差异代谢物在298例慢性肝炎、肝硬化和肝癌病人血清样本中检测,发现甜菜碱和丙酰肉碱联合对原发性肝癌有良好的诊断能力。通过另一批血清样本的外部验证,进一步证实了上述两种代谢物在肝癌中的诊断潜力,与肝癌标志物甲胎蛋白有很好的互补性。

原文摘要:

Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics

Qiang Huang, Yexiong Tan, Peiyuan Yin, Guozhu Ye, Peng Gao, Xin Lu,Hongyang Wang, and Guowang Xu

Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and β-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein.