Nuclear magnetic resonance-based metabolomics and metabolic pathway networks from patient-matched esophageal carcinoma, adjacent noncancerous tissues and urine

World J Gastroenterol. 2019 Jul 7;25(25):3218-3230. doi: 10.3748/wjg.v25.i25.3218.

Abstract

Background: Several studies have demonstrated a correlation between esophageal cancer (EC) and perturbed urinary metabolomic profiles, but none has described the correlation between urine metabolite profiles and those of the tumor and adjacent esophageal mucosa in the same patient.

Aim: To investigate how urinary metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors.

Methods: Nuclear magnetic resonance-based metabolomics were applied to esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched urine samples.

Results: Analysis revealed that specific metabolite changes overlapped across both metrics, including glucose, glutamate, citrate, glycine, creatinine and taurine, indicating that the networks for metabolic pathway perturbations in EC, potentially involved in but not limited to disruption of fatty acid metabolism, glucose and glycolytic metabolism, tricarboxylic acid cycle and glutaminolysis. Additionally, changes in most urinary biomarkers correlated with changes in biomarker candidates in EC tissues, implying enhanced energy production for rapid cell proliferation.

Conclusion: Overall, these associations provide evidence for distinct metabolic signatures and pathway disturbances between the tumor tissues and urine of EC patients, and changes in urinary metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues. Further investigation is needed to validate these initial findings using larger samples and to establish the underlying mechanism of EC progression.

Keywords: Esophageal cancer; Metabolic pathways; Metabolites; Nuclear magnetic resonance-based metabolomics; Tumor tissue; Urine.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / urine
  • Disease Progression
  • Esophageal Mucosa / metabolism*
  • Esophageal Mucosa / pathology
  • Esophageal Mucosa / surgery
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / urine
  • Esophagectomy
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolic Networks and Pathways*
  • Metabolome
  • Metabolomics / methods*
  • Middle Aged
  • Preoperative Period
  • Tumor Microenvironment
  • Urinalysis / methods

Substances

  • Biomarkers, Tumor