血清代谢轮廓分析在评估乙肝肝硬化病程中的应用  

Application of Serum Metabolic Profiling in Evaluating Development of Hepatitis B Virus-induced Cirrhosis

作　　者：杜振华[1] 张磊[2] 刘树业[2] 

机构地区：[1]天津医科大学三中心临床学院,天津300070 [2]天津市第三中心医院,天津市人工细胞重点实验室,天津300170

出　　处：《分析化学》2011年第8期1279-1283,共5页Chinese Journal of Analytical Chemistry

摘　　要：采用高效液相色谱-质谱联用(HPLC-MS)作为代谢组学研究平台,分析不同Child-Pugh分级肝硬化病人和健康人群的血清标本,获取代谢轮廓。对数据进行主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA),用各组病例的80%作为训练数据构建疾病的OPLS-DA区分模型,以剩余的20%作为检测数据,观察模型对处于肝硬化不同阶段病例的区分能力,探讨血清代谢轮廓分析在评估乙肝肝硬化病程中的应用价值及其方法。研究表明,由肝硬化A级组、B级组、C级组和健康对照组构建的OPLS-DA模型(R2Y=90.1%,Q2=66.7%)对检测数据的预测准确率达到93.8%,具有很好的判别能力。排除肝癌因素的影响,利用发生肝癌和未发生肝癌的肝硬化A,B,C及对照组(共7组)构建的OPLS-DA模型(R2Y=96.6%,Q2=56.7%),对检测组数据的预测准确率甚至接近100%。研究表明:由血清代谢轮廓构建的OPLS-DA区分模型可以灵敏地区分肝硬化的临床分级,区分肝癌的发生与否。说明本方法在乙肝肝硬化的病程评估中有良好的应用前景。The metabolic profiling was gotten through analyzing serum specimens from people of healthy control group,hepatitis B virus（HBV）-induced cirrhosis Child-Pugh grade A,B and C groups with high performance liquid chromatography combined with LTQ Orbitrap XL mass spectrometer（HPLC-LTQ Orbitrap XL MS） platform respectively.Then the data were analyzed with principle component analysis（PCA） and orthogonal partial lease square-discriminate analysis（OPLS-DA） to discover the potential information underlying the metabolic profiling.After that 80% of each group,as the training set,was used to construct the OPLS-DA mode,while the left 20%,as the testing set,was used to validate the mode.The result showed that the OPLS-DA mode（R2Y=90.1%,Q2=66.7%） constructed from the serum metabolic profiling of Child-Pugh grade A,B,C groups and healthy control group could discriminate the four groups with a correct rate 93.7%.In order to exclude the effects of the hepatocellular carcinoma（HCC） happened in some patients,the OPLS-DA mode（R2Y=96.6%,Q2=56.7%） was constructed again with 7 groups including healthy control group,Child-Pugh grades A,B,C with HCC groups and without HCC groups,and the new mode had a correct rate 100% when used in the testing set.The results suggest that the metabolic profiling of serum can be used to evaluate the proceeding of HBV-induced liver diseases including different Child-Pugh grades and HCC sensitively and accurately,which means the metabolic profiling can be a promising method in evaluating the development of HBV-associated cirrhosis.

关 键 词：代谢轮廓分析 主成分分析 正交偏最小二乘判别分析 代谢组学 肝癌 乙肝肝硬化 

分 类 号：R575.2[医药卫生—消化系统]