■泰国人群的全球液相色谱质谱(LC-MS)分析先前已在Opisthorchisviverrini诱导的胆管癌(CCA)中确定了尿代谢特征,主要以酰基肉碱的干扰为特征,胆汁酸,类固醇,嘌呤代谢.然而,在单个实验中通过LC-MS检测生物样品中的数千个分析物潜在地引入错误发现。为了验证这些观察到的代谢扰动,来自同一人群的第二个验证数据集以类似的方式进行了分析.
■使用反相高效液相色谱质谱来获取从KhonKaen招募的98份尿液样本(来自46名健康志愿者和52名CCA患者)的全球光谱图,泰国东北部(全球CCA发病率最高)。
■代谢产物在CCA患者的尿中差异表达。梗阻性黄疸的存在会影响高尿胆汁酸的消除。与非黄疸CCA患者相关的尿液代谢组显示出独特的模式,与已发表的研究相似但不完全相同。对于CCA的存在,一组10种代谢物的诊断准确率为93.4%,曲线下面积值为98.8%(CI=96.3%-100%)。
■CCA尿代谢组的总体表征在本验证研究中确定了几种具有生物学意义的代谢产物。对判别代谢物的诊断效用的分析显示出出色的诊断潜力。需要进一步的更大规模的研究来在国际上证实这些发现,特别是与零星的CCA相比,与肝吸虫感染无关。
UNASSIGNED: Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population has previously identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid, and purine metabolism. However, the detection of thousands of analytes by LC-MS in a biological sample in a single experiment potentially introduces false discovery errors. To verify these observed metabolic perturbations, a second validation dataset from the same population was profiled in a similar fashion.
UNASSIGNED: Reverse-phase ultra-performance liquid-chromatography mass spectrometry was utilised to acquire the global spectral profile of 98 spot urine samples (from 46 healthy volunteers and 52 CCA patients) recruited from Khon Kaen, northeast Thailand (the highest incidence of CCA globally).
UNASSIGNED: Metabolites were differentially expressed in the urinary profiles from CCA patients. High urinary elimination of bile acids was affected by the presence of obstructive jaundice. The urine metabolome associated with non-jaundiced CCA patients showed a distinctive pattern, similar but not identical to published studies. A panel of 10 metabolites achieved a diagnostic accuracy of 93.4% and area under the curve value of 98.8% (CI = 96.3%-100%) for the presence of CCA.
UNASSIGNED: Global characterisation of the CCA urinary metabolome identified several metabolites of biological interest in this validation study. Analyses of the diagnostic utility of the discriminant metabolites showed excellent diagnostic potential. Further larger scale studies are required to confirm these findings internationally, particularly in comparison to sporadic CCA, not associated with liver fluke infestation.