Targeted metabolic profiling of hepatocellular carcinoma and hepatitis C using LC-MS/MS.
Targeted metabolic profiling of hepatocellular carcinoma and hepatitis C using LC-MS/MS.
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DOI：
10.1002/elps.201300029
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发表时间：
2013-10
期刊：
影响因子：
2.9
通讯作者：
Raftery, Daniel
中科院分区：
文献类型：
--
作者：
Baniasadi, Hamid;Gowda, G. A. Nagana;Gu, Haiwei;Zeng, Ao;Zhuang, Shui;Skill, Nicholas;Maluccio, Mary;Raftery, Daniel
丙型肝炎病毒（HCV）感染的肝脏是一个全球性的健康问题，是发展为肝细胞癌（HCC）的主要危险因素。需要灵敏的方法来改善和早期检测HCC，这将提供更好的治疗选择。高风险人群（HCV患者）和HCC患者的代谢谱提供了对肝癌发生过程和早期癌症检测的可能生物标志物的见解。采用基于液相色谱-串联质谱（LC-MS/MS）的靶向方法，对HCC（n=30）和HCV（n=22）患者的73种血液代谢物进行定量分析。73种靶向代谢物中有16种存在显著差异（p < 0.05），并且它们的水平在HCC和HCV之间的变化高达3.3倍。使用显示最低p值的这16种代谢物中的4种（蛋氨酸、5-羟甲基-2 ′-脱氧尿苷、N2，N2-二甲基鸟苷和尿酸），使用偏最小二乘判别分析开发和内部验证分类模型。该模型具有较高的分类准确性，区分两组的灵敏度，特异性和受试者工作特征曲线下的面积分别为97%，95%和0.98，分别。基于16种生物标志物候选物，鉴定了许多受干扰的代谢途径，包括氨基酸、嘌呤和核苷酸代谢。这些结果提供了一种有前途的方法来区分丙型肝炎患者，谁是在高风险发展为肝癌，从那些谁已经进展为肝癌。研究结果还提供了对HCC和HCV之间代谢改变的见解。
Hepatitis C virus (HCV) infection of the liver is a global health problem and a major risk factor for the development of hepatocellular carcinoma (HCC). Sensitive methods are needed for the improved and earlier detection of HCC, which would provide better therapy options. Metabolic profiling of the high risk population (HCV patients) and those with HCC provides insights into the process of liver carcinogenesis and possible biomarkers for earlier cancer detection. Seventy-three blood metabolites were quantitatively profiled in HCC (n=30) and cirrhotic HCV (n=22) patients using a targeted approach based on liquid chromatography resolved tandem mass spectrometry (LC-MS/MS). Sixteen of the 73 targeted metabolites differed significantly (p < 0.05) and their levels varied up to a factor of 3.3 between HCC and HCV. Four of these 16 metabolites (methionine, 5-hydroxymethyl-2′-deoxyuridine, N2,N2-dimethylguanosine and uric acid) that showed the lowest p-values were used to develop and internally validate a classification model using partial least squares discriminant analysis. The model exhibited high classification accuracy for distinguishing the two groups with sensitivity, specificity and area under the receiver operating characteristic curve of 97%, 95%, and 0.98, respectively. A number of perturbed metabolic pathways including amino acid, purine and nucleotide metabolism were identified based on the 16 biomarker candidates. These results provide a promising methodology to distinguish cirrhotic HCV patients, who are at high risk to develop HCC, from those who have already progressed to HCC. The results also provide insights into the altered metabolism between HCC and HCV.
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影响因子：
2
作者：
Djukovic, Danijel;Baniasadi, Hamid R.;Raftery, Daniel
通讯作者：
Raftery, Daniel
DOI：
10.1016/j.bpg.2012.09.009
发表时间：
2012-08-01
影响因子：
3.2
作者：
Maasoumy, Benjamin;Wedemeyer, Heiner
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Taylor-Robinson, Simon D.
影响因子：
5.1
作者：
Gowda GA;Zhang S;Gu H;Asiago V;Shanaiah N;Raftery D
通讯作者：
Raftery D
影响因子：
254.7
作者：
Siegel, Rebecca;Naishadham, Deepa;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin