Urinary Metabolomics to Identify a Unique Biomarker Panel for Detecting Colorectal Cancer: A Multicentre Study

Background:Population-based screening programs are credited with earlier colorectal cancer (CRC) diagnoses and treatment initiation which reduce mortality rates and improve patient health outcomes. However, recommended screening methods are unsatisfactory as they are invasive, resource intensive, suffer from low uptake, or have poor diagnostic performance. Our goal was to identify a urine metabolomic-based biomarker panel for the detection of CRC that has the potential for global population-based screening. Methods:Prospective urine samples were collected from study participants. Based upon colonoscopy and histopathology results, 342 participants (CRC, 171; healthy controls, 171) from two study sites (e.g., Canada, United States) were included in the analyses. Targeted liquid chromatography-mass spectrometry was performed to quantify 140 highly valuable metabolites in each urine sample. Potential biomarkers for CRC were identified by comparing the metabolomic profiles from CRC versus controls. Multiple models were constructed leading to a good separation of CRC from controls. Results: A panel of 17 metabolites was identified as possible biomarkers for CRC. Using only two of the selected metabolites, namely diacetylspermine and kynurenine, a predictor for detecting CRC was developed with an AUC of 0.864, a specificity of 80.0% and a sensitivity of 80.0%. Conclusions: We present a potentially "universal" metabolomic biomarker panel for CRC independent of cohort clinical features based on a North American population. Further research is needed to confirm the utility of the profile in a prospective, population-based CRC screening trial. Impact: A urinary metabolomic biomarker panel was identified for CRC with the potential of clinical application.