Urine-NMR metabolomics for screening of advanced colorectal adenoma and early stage colorectal cancer

Sci Rep. 2019 Mar 18;9(1):4786. doi: 10.1038/s41598-019-41216-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / pathology
  • Adenoma / urine*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine / urine
  • Aminoisobutyric Acids / urine
  • Biomarkers, Tumor / urine*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / urine*
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Metabolome*
  • Metabolomics / methods
  • Middle Aged
  • Neoplasm Invasiveness
  • Taurine / urine

Substances

  • Aminoisobutyric Acids
  • Biomarkers, Tumor
  • Taurine
  • Alanine