Abstract
Metabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests.
Highlights
Colorectal cancer (CRC) diagnosis is mainly based on invasive, costly, and time-consuming methods, as noninvasive methods, such as stool-based tests or the carcinoembryonic antigen (CEA) test, lack sensitivity and specificity [1,2,3]
The present study aimed to analyze by 1 H-NMR spectroscopy the urine metabolomics profile of colorectal cancer patients (CRC) patients and cancer-free controls, to identify a possible specific set of metabolic biomarkers that could be proposed as a noninvasive diagnostic tool to identify CRC patients
0.187 obtained demonstrated that the CRC group showed increased relative levels of acetoacetate, creatinine, Metabolites were selected on VIP > 1 based on Orthogonal Partial Least Squares Discriminant and histamine, whereas creatine, phenylacetylglycine, and tryptophan levels were lower compared to Analysis (OPLS-DA) . a Relative concentrations were calculated by normalization of the molar the C group
Summary
Colorectal cancer (CRC) diagnosis is mainly based on invasive, costly, and time-consuming methods (e.g., endoscopic, histological, and radiographic techniques), as noninvasive methods, such as stool-based tests (e.g., fecal occult blood test, FOBT) or the carcinoembryonic antigen (CEA) test, lack sensitivity and specificity [1,2,3]. Metabolomics analysis of samples from CRC patients has led to the identification of several molecules expressed, and the monitoring of their fluctuations is emerging as an important way to detect the early stages of CRC [6,8,9,10,11,12] On this basis, the present study aimed to analyze by 1 H-NMR spectroscopy the urine metabolomics profile of CRC patients and cancer-free controls, to identify a possible specific set of metabolic biomarkers that could be proposed as a noninvasive diagnostic tool to identify CRC patients
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