Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy

In small cell lung cancer (SCLC), oxidative stress disrupts redox balance and contributes to tumor progression and treatment resistance through DNA damage, inflammation, and tumorigenesis. Thiol compounds such as glutathione (GSH) and cysteine (CyS) together with their oxidized forms (GSSG and CySS) serve as markers of oxidative stress. The aim of this study was to investigate changes in GSH/GSSG and CyS/CySS ratios during chemotherapy and evaluate their potential as prognostic indicators in SCLC.

In this longitudinal study, redox biomarkers (GSH/GSSG and CyS/CySS ratios) were investigated in 60 stage III/IV SCLC patients receiving cisplatin-etoposide chemotherapy. Plasma samples were collected before chemotherapy, after two cycles and after four cycles and analyzed by LC-MS/MS.

Significant redox changes were observed during chemotherapy. The GSH/GSSG ratio decreased after two cycles (p = 0.029) and increased after four cycles (p = 0.002). The same trend was observed for CyS/CySS dynamics (p = 0.031 and p = 0.030, respectively). The Survivors showed a recovery of the redox balance, while the deceased patients showed persistently lower ratios. Kaplan-Meier analysis showed that a higher GSH/GSSG ratio before treatment (p = 0.037) predicted better survival. A positive correlation was found between GSH/GSSG and CyS/CySS ratios (ρ = 0.306, p = 0.019).

This study demonstrates that redox imbalance reflected in GSH/GSSG and CyS/CySS ratios is an important factor for SCLC treatment response and survival. Higher GSH/GSSG ratios before treatment are associated with improved survival, indicating the potential of redox markers as prognostic tools in SCLC.