Urinary Metabolic Biomarkers of Hepatocellular Carcinoma in an Egyptian Population: A Validation Study
Urinary Metabolic Biomarkers of Hepatocellular Carcinoma in an Egyptian Population: A Validation Study
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DOI：
10.1021/pr101096f
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Taylor-Robinson, Simon D.
中科院分区：
文献类型：
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作者：
Shariff, Mohamed I. F.;Gomaa, Asmaa I.;Taylor-Robinson, Simon D.
随着代谢组学的出现，肝细胞癌患者的生物流体分析研究激增。这些研究中的大多数都是在单一的土著人群中进行的，这使得候选代谢物生物标志物的广泛适用性变得困难。这里介绍的是一个尿质子核磁共振波谱研究主要是丙型肝炎病毒感染的埃及肝细胞癌患者，这证实了以前的研究结果，主要是乙型肝炎病毒感染的尼日利亚肝细胞癌患者。使用多变量统计分析，在正交信号校正偏最小二乘判别分析的形式，区分肿瘤患者与健康对照和肝硬化患者的技术的灵敏度和特异性分别为100%/94%和81%/71%。鉴别代谢物包括甘氨酸、三甲胺-N-氧化物、马尿酸盐、柠檬酸盐、肌酐、肌酸和肉毒碱。该代谢谱与尼日利亚受试者队列中鉴定的谱相似，表明肿瘤对生理学、能量产生和异常染色体甲基化的影响。这是第一个研究，以确定类似的改变尿代谢谱的肝细胞癌在两个病因和种族不同的人群，这表明，改变代谢作为肿瘤发生的结果是独立的这两个因素。
The advent of metabonomics has seen a proliferation of biofluid profiling studies of patients with hepatocellular carcinoma. The majority of these studies have been conducted in single indigenous populations making the widespread applicability of candidate metabolite biomarkers difficult. Presented here is a urinary proton nuclear magnetic resonance spectroscopy study of mainly hepatitis C virus infected Egyptian patients with hepatocellular carcinoma, which corroborates findings of a previous study from our group of mainly hepatitis B-infected Nigerian patients with hepatocellular carcinoma. Using multivariate statistical analysis, in the form of orthogonal signal-corrected partial least squared discriminant analysis, the sensitivity and specificity of the technique for distinguishing patients with tumors from healthy controls and patients with cirrhosis was 100%/94% and 81%/71%, respectively. Discriminatory metabolites included glycine, trimethylamine-N-oxide, hippurate, citrate, creatinine, creatine, and carnitine. This metabolic profile bears similarity to profiles identified in the Nigerian cohort of subjects indicative of tumor effects on physiology, energy production, and aberrant chromosomal methylation. This is the first study to identify similarly altered urine metabolic profiles of hepatocellular carcinoma in two etiologically and ethnically distinct populations, suggesting that altered metabolism as a result of tumorogenesis is independent of these two factors.