Redox forms of glutathione mark the aggressiveness of stomach cancer
Authors: I. Goroshinskaya, E. Surikova, E. Frantsiyants, I. Neskubina, Y. Pogorelova, D. Medvedeva, A. Maslov, O. Kit
Journal: Annals of Oncology (2018)

Introduction: The redox status is important for the gastric epithelium function. The purpose of the study was to compare levels of reduced and oxidized glutathione and thiol status in stomach tumors of various histological types and grades. Methods: The levels of reduced (GSH) and oxidized (GSSG) glutathione and thiol status were determined by ELISA in tumor, peritumoral and visually intact tissues obtained during surgery from 52 patients with stomach cancer: 18 patients – G1-2 adenocarcinoma (AC, T2-4N0-2 M0); 8 – G3 AC (T2-4N0-3M0); 14 – combined gastric lesions (CGL), AC with signet ring cell fragments (T3-4N0-3M0-1); 6 – signet ring cell cancer (SRCC, T1-4N1-3M0-1); 6 – patients with a component of undifferentiated cancer, G4 (T2-4N1-3M0-1). The coefficient of GSH and GSSG was calculated (C=GSH/GSSG•10-3). The data were analyzed using Statistika 6.0 program and Student's t-test. Results: With a decrease in the degree of AC differentiation, there was an increase in GSH levels in the tumor tissue and the peritumoral zone with the maximum in G4: 29.9% higher (p = 0.0112) in tumors and 40.7% higher (p = 0.0026) in peritumoral zone in comparison with G1-2 AC. GSH in all tissues of patients with CGL was 13-19% higher than in patients with G1-2 AC (p < 0.05). Tumor GSH levels in G3 AC and SRCC exceeded the values in visually intact tissues by 19.9% and 17% respectively (p = 0.02-0.05). The levels in visually intact tissues in SRCC were 17.3% lower than in G1-2 AC (p = 0.0006) and 27.7% lower than in CGL (p = 0.0074). A significant decrease in tumor GSSG levels was registered in SRCC only: 27.5% lower than in G1-2 AC and 30.3% lower than in G3 AC (p = 0.0021-0.0029). Patients with undifferentiated tumors (G4 AC) had increased GSH in all studied tissues: in tumor by 29.9% (p = 0.0112); in peritumoral zone by 40.7% (p = 0.0026); in visually intact tissues by 22.5% with increased GSSG – by 25.5% (p = 0.0001) compared to G1-2 AC, as well as compared to SRCC (p = 0.02-0.000002). G4 AC were characterized by a sharp increase in the thiol status in tumor tissues – by 80.2% and 89.9% higher than in visually intact and peritumoral tissues (p = 0.0012-0.0038), 72.6% higher than in G1-2 AC (p = 0.00002), 95.7% higher than in G3 AC (p = 0.00018), and 68-69% higher than in SRCC and CGL (p = 0.0056-0.0232). The coefficient of GSH and GSSG was the most informative. In comparison with the value in patients with G1-2 AC, the GSH/GSSG•10-3 index was 14.1% higher (p = 0.0844) in patients with G3 AC, by 34.5-35.6% (p = 0.0021-0.0345) with G4 AC and CGL, and by 75.1% (p = 0.001) in patients with SRCC. Conclusion: Reduction of AC differentiation (in the row G1-2, G3, G4) and a change of histological tumor type (AC, SPL and SRCC), i.e. an increase in tumor aggressiveness, is accompanied by the enhancement of reduction processes in tumor tissue, as evidenced by the statistically significant increase in the GSH/GSSG coefficient and a sharp increase in the thiol status in the case of G4 AC. Changes in GSH and GSSG levels were found even in some visually intact tissues.