Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy
Abstract 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 f...
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| Format: | Article |
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-03251-2 |
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| author | Azra Guzonjić Milkica Crevar Ivana Simić Natalija Samardzić Vesna Ćeriman Krstić Jelena Kotur Stevuljević Dragana Jovanović |
| author_facet | Azra Guzonjić Milkica Crevar Ivana Simić Natalija Samardzić Vesna Ćeriman Krstić Jelena Kotur Stevuljević Dragana Jovanović |
| author_sort | Azra Guzonjić |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-aefb2c103b6248d9b96ce55c56a41e1e |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-aefb2c103b6248d9b96ce55c56a41e1e2025-08-20T03:42:57ZengSpringerDiscover Oncology2730-60112025-07-0116111310.1007/s12672-025-03251-2Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapyAzra Guzonjić0Milkica Crevar1Ivana Simić2Natalija Samardzić3Vesna Ćeriman Krstić4Jelena Kotur Stevuljević5Dragana Jovanović6Faculty of Pharmacy, Department for Medical Biochemistry, University of BelgradeFaculty of Pharmacy, Department of Pharmaceutical Chemistry, University of BelgradeMerck Sharp & Dohme d.o.o, Medical AffairsClinic for pulmonology, University Clinical Center of SerbiaClinic for pulmonology, University Clinical Center of SerbiaFaculty of Pharmacy, Department for Medical Biochemistry, University of BelgradeInternal Medicine Clinic “Akta Medica”, Cara Nikolaja IIAbstract 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.https://doi.org/10.1007/s12672-025-03251-2Oxidative stressLung cancerRedox imbalancePrognostic biomarkers |
| spellingShingle | Azra Guzonjić Milkica Crevar Ivana Simić Natalija Samardzić Vesna Ćeriman Krstić Jelena Kotur Stevuljević Dragana Jovanović Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy Discover Oncology Oxidative stress Lung cancer Redox imbalance Prognostic biomarkers |
| title | Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy |
| title_full | Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy |
| title_fullStr | Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy |
| title_full_unstemmed | Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy |
| title_short | Alterations in GSH/GSSG and CyS/CySS redox status in small cell lung cancer patients undergoing chemotherapy |
| title_sort | alterations in gsh gssg and cys cyss redox status in small cell lung cancer patients undergoing chemotherapy |
| topic | Oxidative stress Lung cancer Redox imbalance Prognostic biomarkers |
| url | https://doi.org/10.1007/s12672-025-03251-2 |
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