Abstract

Background: 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. Methods: 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). Results: 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. Conclusion: 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%).

Highlights

  • Colorectal cancer (CRC) is a major public health concern

  • Correlations were calculated by encoding those patients who are likely to have adenomatous polyps and require colonoscopy as “1” and those that do not as “0”

  • Higher concentrations of the 3 metabolites were inversely correlated with the presence of adenomatous polyps

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Summary

Introduction

Colorectal cancer (CRC) is a major public health concern. It is ranked as the third most frequent form of cancer with an age-standardized incidence rate of 17.2 per 100,000 population making it responsible for almost 8.5% of all deaths due to cancer [1]. 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. Conclusion: 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 (

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