Abstract
Although colorectal cancer (CRC) is considered one of the most preventable cancers, no non-invasive, accurate diagnostic tool to screen CRC exists. We explored the potential of urine nuclear magnetic resonance (NMR) metabolomics as a diagnostic tool for early detection of CRC, focusing on advanced adenoma and stage 0 CRC. Urine metabolomics profiles from patients with colorectal neoplasia (CRN; 36 advanced adenomas and 56 CRCs at various stages, n = 92) and healthy controls (normal, n = 156) were analyzed by NMR spectroscopy. Healthy and CRN groups were statistically discriminated using orthogonal projections to latent structure discriminant analysis (OPLS-DA). The class prediction model was validated by three-fold cross-validation. The advanced adenoma and stage 0 CRC were grouped together as pre-invasive CRN. The OPLS-DA score plot showed statistically significant discrimination between pre-invasive CRN as well as advanced CRC and healthy controls with a Q2 value of 0.746. In the prediction validation study, the sensitivity and specificity for diagnosing pre-invasive CRN were 96.2% and 95%, respectively. The grades predicted by the OPLS-DA model showed that the areas under the curve were 0.823 for taurine, 0.783 for alanine, and 0.842 for 3-aminoisobutyrate. In multiple receiver operating characteristics curve analyses, taurine, alanine, and 3-aminoisobutyrate were good discriminators for CRC patients. NMR-based urine metabolomics profiles significantly and accurately discriminate patients with pre-invasive CRN as well as advanced CRC from healthy individuals. Urine-NMR metabolomics has potential as a screening tool for accurate diagnosis of pre-invasive CRN.
Highlights
Colorectal Cancer (CRC) is one of the most common causes of cancer-related deaths globally
The characteristics of both patients and healthy controls are summarized in carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) levels for patients with stage I to IV colorectal cancer (CRC) and for healthy controls were assessed
We analyzed all the Nuclear magnetic resonance (NMR) spectroscopy-based urine metabolic profiles and performed multivariate statistical analyses to discriminate between colorectal neoplasia (CRN) patients and healthy controls
Summary
Colorectal Cancer (CRC) is one of the most common causes of cancer-related deaths globally. The development of reliable and non-invasive screening tools for early stage CRC and precancerous lesions, such as adenoma, is indispensable. An unacceptably wide range or the lack of sensitivity and specificity of the FOBT has hampered its clinical application in CRC diagnosis, especially for precancerous lesions[8] Tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are commonly used in the clinic. The development of a low-cost, easy, and accurate diagnostic approach for the detection of advanced adenoma and early stage CRC would be essential for complete recovery of the patient and to reduce medical expenses. A few metabolic markers are consistently found in CRC, but metabolic profiles of patients with early stage CRC including precancerous lesions remain poorly understood and warrant further investigation due to the non-invasive nature of the approach[15,16]. The major finding of this research was the identification of stage I and II specific biomarkers indicating that several metabolisms including those from amino acids, glycolysis, the TCA cycle, the urea cycle, choline metabolism, and gut microflora metabolism were highly active in these stages
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