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Background <p>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.</p> Materials and methods <p>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.</p> Results <p>Significant redox changes were observed during chemotherapy. The GSH/GSSG ratio decreased after two cycles (<i>p</i> = 0.029) and increased after four cycles (<i>p</i> = 0.002). The same trend was observed for CyS/CySS dynamics (<i>p</i> = 0.031 and <i>p</i> = 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 (<i>p</i> = 0.037) predicted better survival. A positive correlation was found between GSH/GSSG and CyS/CySS ratios (ρ = 0.306, <i>p</i> = 0.019).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月30日

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  • Azra Guzonjić,
  • Milkica Crevar,
  • Ivana Simić,
  • Natalija Samardzić,
  • Vesna Ćeriman Krstić,
  • Jelena Kotur Stevuljević,
  • Dragana Jovanović

摘要

Background

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.

Materials and methods

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.

Results

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).

Conclusions

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.