Metabolic profile of the Warburg effect as a tool for molecular prognosis and diagnosis of cancer

Expert Rev Mol Diagn. 2022 Apr;22(4):439-447. doi: 10.1080/14737159.2022.2065196. Epub 2022 Apr 12.

Abstract

Introduction: Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells.

Areas covered: This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways.

Expert opinion: In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.

Keywords: Biomarker; Warburg effect; cancer; diagnosis; metabolism; molecular prognosis.

Publication types

  • Review

MeSH terms

  • Amino Acids, Branched-Chain / metabolism
  • Glucose / metabolism
  • Glutamine* / metabolism
  • Humans
  • Metabolome
  • Neoplasms* / diagnosis
  • Neoplasms* / metabolism
  • Proline / metabolism

Substances

  • Amino Acids, Branched-Chain
  • Glutamine
  • Proline
  • Glucose