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

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.

Oxidative Stress and DNA Damage Markers in Colorectal Cancer

“…A comprehensive study of 150 patients with CRC who underwent surgery analyzed OS parameters (MDA and 4-HNE) in peripheral and mesenteric blood according to four tumor stages (I-IV). The authors observed that levels of both OS markers increased with tumor stage [ 58 ], in line with previous results published by our group [ 28 ].…”

“…Dusak et al also reported decreased levels of GSH in the serum of 25 CRC patients with respect to healthy controls [ 16 ]. Serum levels of GSH and GSSG and the GSSG/GSH ratio have been pointed to as potentially effective TMs, not only in CRC, but in other types of cancer [ 28 ]. Rasool et al, in a study of 50 CRC patients and 20 controls, detected lower levels of CAT and GSH in the serum of patients with respect to controls, which, once again, is in accordance with our results [ 18 ].…”

“…Although elevated levels of both TM CEA and CA 19.9 are generally used in prognosis in clinical practice [ 43 ], a comparison with OS shows that their sensitivity is considerably low, especially in the case of CA 19.9 [ 28 ].…”

S-glutathionylation of Hsp90 enhances its degradation and correlates with favorable prognosis of breast cancer

“…In general, the ratio of GSH/GSSG is about 100:1 under physiological condition [ 34 ]. Decreased level of GSH in cancer cells results is often associated with defective response to oxidative stress [ 35 ]. Since S-glutathionylation is a reversible modification on cysteine residues of proteins, evaluating the levels of blood GSH and GSH/GSSG could well reflect the status of glutathionylated Hsp90 in tumor tissues.…”

Modeling Reactive Species Metabolism in Colorectal Cancer for Identifying Metabolic Targets and Devising Therapeutics

“…The glutathione redox status in terms of GSH/GSSG is an important tumour biomarker of CRC [55] and can be used in non-invasive CRC diagnosis. GSH/GSSG of the CRC model reduced after integrating the RS module to the CRC model due to the increase in the flux activity of GSSG producing reactions.…”