Distinct Urinary Metabolic Profile of Human Colorectal Cancer
Distinct Urinary Metabolic Profile of Human Colorectal Cancer
复制标题
人类结直肠癌的独特尿液代谢特征
DOI：
10.1021/pr201001a
复制
发表时间：
2012-02-01
影响因子：
4.4
通讯作者：
Jia, Wei
中科院分区：
文献类型：
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作者：
Cheng, Yu;Xie, Guoxiang;Jia, Wei
在可治愈的早期阶段，与结直肠癌(CRC)直接相关的全谱代谢异常对于开发和部署分子诊断和治疗方法至关重要，这些方法将显著提高患者的存活率。我们最近报道了一项针对结直肠癌受试者(n=60)和健康对照组(n=63)的尿代谢组学研究，其中确定了一组尿代谢物标记物。在这里，我们报告了第二次尿代谢组学研究，使用气相色谱飞行时间质谱仪和超高效液相色谱四极飞行时间质谱仪对更大的结直肠癌(n=101)和健康受试者(n=103)进行了研究。与我们以前的发现一致，我们在结直肠癌患者中观察到了许多异常的代谢途径，如糖酵解、TCA循环、尿素循环、嘧啶代谢、色氨酸代谢、多胺代谢以及肠道微生物宿主共代谢。我们的发现证实了结直肠癌患者独特的尿液代谢足迹，其特征是肠道微生物宿主共代谢产生的代谢物水平改变。选择了一组代谢物标记物，包括柠檬酸盐、马尿酸、对甲酚、2-氨基丁酸盐、肉豆蔻酸酯、腐胺和犬尿酸，这些标记物能够区分结直肠癌患者和健康人。对这些标记的接收者操作特征曲线(ROC)分析得出训练集和测试集的接收者操作特征曲线(AuC)下的面积分别为0.993和0.998。这些潜在的代谢物标志物为结直肠癌的早期检测提供了一种新的、有前途的分子诊断方法。
A full spectrum of metabolic aberrations that are directly linked to colorectal cancer (CRC) at early curable stages is critical for developing and deploying molecular diagnostic and therapeutic approaches that will significantly improve patient survival. We have recently reported a urinary metabonomic profiling study on CRC subjects (n = 60) and health controls (n = 63), in which a panel of urinary metabolite markers was identified. Here, we report a second urinary metabonomic study on a larger cohort of CRC (n = 101) and healthy subjects (n = 103), using gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry. Consistent with our previous findings, we observed a number of dysregulated metabolic pathways, such as glycolysis, TCA cycle, urea cycle, pyrimidine metabolism, tryptophan metabolism, polyamine metabolism, as well as gut microbial host co-metabolism in CRC subjects. Our findings confirm distinct urinary metabolic footprints of CRC patients characterized by altered levels of metabolites derived from gut microbial host co-metabolism. A panel of metabolite markers,composed of citrate, hippurate, p-cresol, 2-aminobutyrate, myristate, putrescine, and kynurenate was selected, which was able to discriminate CRC subjects from their healthy counterparts. A receiver operating characteristic curve (ROC) analysis of these markers resulted in an area under the receiver operating characteristic curve (AUC) of 0.993 and 0.998 for the training set and the testing set, respectively. These potential metabolite markers provide a novel and promising molecular diagnostic approach for the early detection of CRC.