Deng Lu, Chang David, Foshaug Rae R, Eisner Roman, Tso Victor K, Wishart David S, Fedorak Richard N
Metabolomic Technologies Inc., Edmonton, AB T6N 1G1, Canada.
Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
Metabolites. 2017 Jun 22;7(3):32. doi: 10.3390/metabo7030032.
Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity) mass spectrometry (MS)-based urine metabolomic test for the detection of adenomatous polyps. : Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set) and validated using the remaining 33% samples (blinded testing set). : The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. : Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86%) over current fecal-based tests (<18%).
结直肠癌是全球癌症死亡的主要原因之一。检测并切除结直肠癌的癌前病变——腺瘤性息肉，是筛查的关键。本研究的目的是开发一种临床上可扩展的（高通量、低成本、高灵敏度）基于质谱（MS）的尿液代谢组学检测方法，用于检测腺瘤性息肉。：前瞻性收集了685名参加结直肠癌筛查项目并接受结肠镜检查的参与者的尿液和粪便样本。对通过一维核磁共振波谱法测得的69种尿液代谢物进行统计分析，以确定关键代谢物。随后开发了一种靶向MS检测方法，用于定量尿液中的关键代谢物。使用67%的样本（未设盲训练集）建立了基于MS的腺瘤性息肉尿液代谢组学诊断检测方法，并使用其余33%的样本（设盲测试集）进行验证。：基于MS的尿液代谢组学检测方法识别结肠腺瘤性息肉患者的曲线下面积（AUC）为0.692，优于基于核磁共振波谱法的预测指标，其AUC为0.670。：在此，我们描述了一种临床上可扩展的基于MS的尿液代谢组学检测方法，该方法识别腺瘤性息肉患者的灵敏度（86%）高于目前基于粪便的检测方法（<18%）。
