Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps
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 sensi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-06-01
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| Series: | Metabolites |
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| Online Access: | http://www.mdpi.com/2218-1989/7/3/32 |
| _version_ | 1811326378500423680 |
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| author | Lu Deng David Chang Rae R. Foshaug Roman Eisner Victor K. Tso David S. Wishart Richard N. Fedorak |
| author_facet | Lu Deng David Chang Rae R. Foshaug Roman Eisner Victor K. Tso David S. Wishart Richard N. Fedorak |
| author_sort | Lu Deng |
| collection | DOAJ |
| description | 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%). |
| first_indexed | 2024-04-13T14:49:38Z |
| format | Article |
| id | doaj.art-3e7194f4983645fca2161603832b2ab0 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-04-13T14:49:38Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-3e7194f4983645fca2161603832b2ab02022-12-22T02:42:39ZengMDPI AGMetabolites2218-19892017-06-01733210.3390/metabo7030032metabo7030032Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous PolypsLu Deng0David Chang1Rae R. Foshaug2Roman Eisner3Victor K. Tso4David S. Wishart5Richard N. Fedorak6Metabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaMetabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaMetabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaMetabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaMetabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaDepartment of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, CanadaMetabolomic Technologies Inc., Edmonton, AB T6N 1G1, CanadaBackground: 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%).http://www.mdpi.com/2218-1989/7/3/32colorectal canceradenomatous polypsmetabolomicsmetaboliteurinediagnostic testMSNMR |
| spellingShingle | Lu Deng David Chang Rae R. Foshaug Roman Eisner Victor K. Tso David S. Wishart Richard N. Fedorak Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps Metabolites colorectal cancer adenomatous polyps metabolomics metabolite urine diagnostic test MS NMR |
| title | Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps |
| title_full | Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps |
| title_fullStr | Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps |
| title_full_unstemmed | Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps |
| title_short | Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps |
| title_sort | development and validation of a high throughput mass spectrometry based urine metabolomic test for the detection of colonic adenomatous polyps |
| topic | colorectal cancer adenomatous polyps metabolomics metabolite urine diagnostic test MS NMR |
| url | http://www.mdpi.com/2218-1989/7/3/32 |
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