Urine NMR Metabolomics for Precision Oncology in Colorectal Cancer

Int J Mol Sci. 2022 Sep 22;23(19):11171. doi: 10.3390/ijms231911171.

Abstract

Metabolomics is a fundamental approach to discovering novel biomarkers and their potential use for precision medicine. When applied for population screening, NMR-based metabolomics can become a powerful clinical tool in precision oncology. Urine tests can be more widely accepted due to their intrinsic non-invasiveness. Our review provides the first exhaustive evaluation of NMR metabolomics for the determination of colorectal cancer (CRC) in urine. A specific search in PubMed, Web of Science, and Scopus was performed, and 10 studies met the required criteria. There were no restrictions on the query for study type, leading to not only colorectal cancer samples versus control comparisons, but also prospective studies of surgical effects. With this review, all compounds in the included studies were merged into a database. In doing so, we identified up to 100 compounds in urine samples, and 11 were found in at least three articles. Results were analyzed in three groups: case (CRC and adenomas)/control, pre-/post-surgery, and combining both groups. When combining the case-control and the pre-/post-surgery groups, up to twelve compounds were found to be relevant. Seven down-regulated metabolites in CRC were identified, creatinine, 4-hydroxybenzoic acid, acetone, carnitine, d-glucose, hippuric acid, l-lysine, l-threonine, and pyruvic acid, and three up-regulated compounds in CRC were identified, acetic acid, phenylacetylglutamine, and urea. The pathways and enrichment analysis returned only two pathways significantly expressed: the pyruvate metabolism and the glycolysis/gluconeogenesis pathway. In both cases, only the pyruvic acid (down-regulated in urine of CRC patients, with cancer cell proliferation effect in the tissue) and acetic acid (up-regulated in urine of CRC patients, with chemoprotective effect) were present.

Keywords: NMR; acetic acid; colorectal cancer; metabolomics; pyruvic acid; urine.

Publication types

  • Review

MeSH terms

  • Acetates
  • Acetone
  • Biomarkers
  • Carnitine
  • Colorectal Neoplasms* / metabolism
  • Creatinine
  • Glucose
  • Humans
  • Lysine
  • Metabolomics / methods
  • Precision Medicine
  • Prospective Studies
  • Pyruvic Acid*
  • Threonine
  • Urea

Substances

  • Acetates
  • Biomarkers
  • Acetone
  • Threonine
  • Pyruvic Acid
  • Urea
  • Creatinine
  • Glucose
  • Lysine
  • Carnitine

Grants and funding

This research was funded by Spanish MINECO, project Total2DChrom [RTI2018-098577-B-C21]. M.L. is thankful for her graduate fellowship from the URV PMF-PIPF program [ref. 2019PMF-PIPF-37]. They acknowledge the AGAUR consolidated groups [2017 SGR 1119, 2017 SGR 00628]. IISPV is a member of the CERCA Programme/Generalitat de Catalunya. This article is based upon work from COST Action 805 CA17118, supported by COST (European Cooperation in Science and Technology).