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从模型大鼠到患者的肝癌形成过程的代谢组学研究:有效诊断小肝细胞癌的潜在生物标志物

作者: 邵雪 发布日期: 2012-05-15 阅读次数:
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 背景:本研究的目的是通过非目标代谢组学方法,在大鼠肝细胞癌 疾病模型中找到潜在生物标志物,测试其在诊断人类早期肝癌中的有效性。方法:采用液相色谱-质谱方法进行二乙基亚硝胺诱导的大鼠肝癌模型的血清代谢谱轮廓分析,其组织病理进展过程与人类肝癌是相似的。利用多元数据分析方法识别潜在生物标志物。 结果3个代谢产物,牛磺胆酸、溶血磷酸酰乙醇胺16:0和溶血磷脂酰胆碱22:5被定义为代谢产物标志物,用来区分肝癌形成过程的不同阶段。这些代表肝癌进展过程中代谢异常的代谢产物,同样在患者中也可以找到。在262例肝癌患者、76例肝硬化患者和74例慢性乙型肝炎患者共412份血清标本中,3个代谢产物对于区别小肝癌(直径小于2cm单发)灵敏度为80.5%,特异度为80.1%,分别优于甲胎蛋白(53%灵敏度和64%特异度)。此外,它们也可以有效区分肝癌患者和慢性肝脏疾病患者,灵敏度87.5%,特异度82.3%,分别优于甲胎蛋白(灵敏度61.2%和特异度64%)。结论:这些结果表明代谢组学方法有找到诊断早期肝癌生物标志物的潜能。

 

 

吉林大学第一医院肝胆胰内科  邵雪  摘译

本文首次发表于[2012 Feb;11(2):M111.010694. Epub 2011 Nov 14]

 

Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis

Abstract

BACKGROUND AND AIMS: The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target  metabolomics method, and test their usefulness in early human HCC diagnosis.

METHODS: The serum metabolic profiling of the  diethylnitrosamine - induced rat HCC model, which presents a stepwise histopathological progression  that is similar to human HCC, was  performed  using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilised to identify the potential biomarkers.

RESULTS: Three metabolites,taurocholic acid,lysophosphoethanolamine 16:0 and lysophosphatidylcholine 22:5, were defined as ‘marker metabolites’ which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients.  To test their diagnosis potential 412  sera  from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumour (solitary nodules of less than 2 cm in diameter) patients,  achieved a sensitivity of 80.5% and a specificity of 80.1%  which is better than those  of α- fetoprotein (53% and 64%, respectively).  Moreover, they  were also effective for the discrimination of all HCCs and chronic liver diseases patients, which could achieve a sensitivity of 87.5%  and a specificity of 72.3% , better than those of α- fetoprotein ( 61.2% and 64%).

CONCLUSIONS: These results indicate metabolomics  method has the potential of finding biomarkers for the early diagnosis of HCC

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作者: 邵雪 发布日期: 2012-05-15 阅读次数: