The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer

Int J Mol Sci. 2021 Jun 8;22(12):6183. doi: 10.3390/ijms22126183.

Abstract

The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

Keywords: GSH; GSSG; GSSG/GSH redox state; colorectal cancer; oxidative stress; tumor markers.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Glutathione / chemistry*
  • Glutathione / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*

Substances

  • Biomarkers, Tumor
  • Reactive Oxygen Species
  • Glutathione