背景：肝细胞癌在世界范围内居恶性肿瘤的第五位，通常是由肝硬化发展而来。区分两者的生物标记物是至关重要而又有限的。方法：在本研究中，采用超高效液相色谱质谱(UPLC-MS)-基于代谢组学的方法来描述82例肝癌患者，48例肝硬化患者和90例健康对照者之间血清代谢产物的特征，并比较了UPLC-MS轮廓和甲胎蛋白水平在肝癌诊断中的准确性。 结果：通过多元数据和受试者工作特征（ROC）曲线分析，代谢轮廓分析不仅可以区分患者与健康对照组，并且对于肝硬化和肝癌患者之间的区别有100%的敏感性和特异性。在肝癌患者中有13种潜在生物标记物被鉴定并被认为对关键代谢途径有显著干扰，比如有机酸、磷脂类、脂肪酸、胆汁酸和肠道菌群的代谢。刀豆氨酸琥珀酸做为代谢产物是第一次被鉴定并且在肝硬化患者中显著降低而在肝癌患者中是升高的。此外，鹅脱氧甘胆酸被认为是诊断肝细胞癌及疾病预后的重要指标。结论：单独应用超高效液相色谱质谱联用方法或者联合甲胎蛋白水平检测可能是肝细胞癌早期诊断及高危人群筛查的一种高效而便捷的工具。
吉林大学第一医院肝胆胰内科 邵雪 摘译
本文首次发表于[Journal of Proteome Research，2012，11(2):1217-1227]
Metabonomic Profiles Discriminate Hepatocellular Carcinoma from Liver Cirrhosis by Ultra-performance Liquid Chromatography-mass Spectrometry
Baohong Wang, Deying Chen, Yu Chen, Zhenhua Hu, Min Cao, Qing Xie, Yanfei Chen, Jiali Xu, Shusen Zheng and Lanjuan Li
Background:Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and usually develops in patients with liver cirrhosis (LC). Biomarkers that discriminate HCC from LC are important but are limited.
Methods：In the present study, an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS)-based metabonomics approach was used to characterize serum profiles from HCC (n=82), LC (n=48), and healthy subjects (n=90), and the accuracy of UPLC-MS profiles and alpha-fetoprotein (AFP) levels were compared for their use in HCC diagnosis.
Results：By multivariate data and receiver operating characteristic curves analysis, metabolic profiles were capable of discriminating not only patients from the controls but also HCC from LC with 100% sensitivity and specificity. Thirteen potential biomarkers were identified and suggested that there were significant disturbances of key metabolic pathways, such as organic acids, phospholipids, fatty acids, bile acids, and gut flora metabolism, in HCC patients. Canavaninosuccinate（CSA） was first identified as a metabolite that exhibited a significant decrease in LC and an increase in HCC. In addition, glycochenodeoxycholic acid（GCDCA） was suggested to be an important indicator for HCC diagnosis and disease prognosis.
Conclusion：UPLC-MS signatures, alone or in combination with AFP levels, could be an efficient and convenient tool for early diagnosis and screening of HCC in high-risk populations.
