Distinct Urinary Metabolic Profile of Human Colorectal Cancer

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• 作者：Yu Cheng ; Guoxiang Xie ; Tianlu Chen ; Yunping Qiu ; Xia Zou ; Minhua Zheng ; Binbin Tan ; Bo Feng ; Taotao Dong ; Pingang He ; Linjing Zhao ; Aihua Zhao ; Lisa X. Xu ; Yan Zhang ; Wei Jia
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：February 3, 2012
• 年：2012
• 卷：11
• 期：2
• 页码：1354-1363
• 全文大小：428K
• 年卷期：v.11,no.2(February 3, 2012)
• ISSN：1535-3907

文摘

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鈥揾ost 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鈥揾ost 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.

Keywords:

colorectal cancer; metabonomics; metabolic profiling; gas chromatography time-of-flight mass spectrometry; ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry; urine

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