Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings Journal Article
| Authors: | Zhang, L.; Zheng, J.; Ismond, K. P.; MacKay, S.; LeVatte, M.; Constable, J.; Isaac Alatise, O.; Kingham, T. P.; Wishart, D. S. |
| Article Title: | Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings |
| Abstract: | BACKGROUND: African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE: To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS: Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS: Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS: Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa. © 2023 - IOS Press. All rights reserved. |
| Keywords: | adult; controlled study; aged; unclassified drug; major clinical study; clinical feature; clinical trial; constipation; diarrhea; cancer patient; prospective study; sensitivity and specificity; colorectal cancer; biological marker; metabolism; cancer screening; creatinine; tumor marker; colorectal neoplasms; creatinine urine level; colonoscopy; colorectal tumor; tandem mass spectrometry; high performance liquid chromatography; urinalysis; observational study; chromatography, liquid; protein urine level; liquid chromatography; glutamic acid; early detection of cancer; aspartic acid; colorectal cancer screening; receiver operating characteristic; kynurenine; cancer biomarkers; water solubility; logistic regression; metabolomics; limit of detection; liquid chromatography-mass spectrometry; procedures; point of care testing; body weight loss; spermine; colorectal polyp; betaine; humans; human; male; female; article; biomarkers, tumor; early cancer diagnosis; urine sampling; nigerian; metabolic fingerprinting; metabolomic profiling; urine test; 3 (3 hydroxyphenyl) 3 hydroxypropionic acid; 4 hydroxyhippurate; hippuric acid; hydracrylic acid; n1 n12 diacetylspermine; feature selection algorithm |
| Journal Title: | Cancer Biomarkers |
| Volume: | 36 |
| Issue: | 1 |
| ISSN: | 1574-0153 |
| Publisher: | IOS Press |
| Date Published: | 2023-01-01 |
| Start Page: | 17 |
| End Page: | 30 |
| Language: | English |
| DOI: | 10.3233/cbm-220034 |
| PUBMED: | 35871322 |
| PROVIDER: | scopus |
| PMCID: | PMC10627333 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2023 -- Source: Scopus |
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