Salivary gamma-glutamyltransferase activity as an indicator of redox homeostasis in breast cancer

Abstract Objectives One of the main participants in maintaining the redox balance is glutathione (GSH), the metabolism of which directly depends on the activity of gamma-glutamyltransferase (GGT), and the content of amino acids cysteine (Cys), methionine (Met), glutamine (Gln), glutamic acid (Glu), and glycine (Gly). This work aimed to investigate the relationship between salivary GGT activity in patients with breast cancer and the state of redox homeostasis. Methods The case-control study included volunteers with breast cancer (n=660), non-malignant breast pathologies (n=134), and a control group (n=127). Analysis of GGT activity and amino acid content in saliva was performed in all patients strictly before treatment, and in 139 patients, the study was repeated 4 weeks after surgical treatment. GGT activity was determined by the Zaits-Persin kinetic method. The concentration of amino acids (Cys, Met, Gln, Glu, and Gly) was determined using high-performance liquid chromatography. Results In breast cancer and fibroadenomas, antioxidant protection was activated and salivary GGT levels increased (+5.6 % in fibroadenomas, +11.3 % in breast cancer, p<0.0001). The highest salivary GGT activity was observed in the luminal hormone-negative breast cancer subgroups (+19.7 %, p<0.0001). This may indicate the sufficiency of metabolic resources to activate the antioxidant system in less aggressive luminal subtypes. In the non-luminal (+12.4 %, р=0.0054) and TNBC (+17.1 %, p<0.0001) subgroups, salivary GGT activity was close to normal values. Probably, in a more aggressive process, with depletion of biological resources, and more pronounced metabolic reprogramming of cancer cells, GSH synthesis is sharply reduced, which is expressed in a change in the amino acid balance. After surgery, salivary GGT activity decreased with the preservation of the residual metabolic pattern of the corresponding breast cancer phenotype. Conclusion The analysis of salivary GGT activity serves as a valuable tool for elucidating metabolic changes associated with breast cancer, including its potential application in post-treatment monitoring.