接受化疗的小细胞肺癌患者谷胱甘肽/氧化型谷胱甘肽和半胱氨酸/胱氨酸氧化还原状态的改变

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

作者信息

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

机构信息

Faculty of Pharmacy, Department for Medical Biochemistry, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia.

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia.

出版信息

Discov Oncol. 2025 Jul 30;16(1):1445. doi: 10.1007/s12672-025-03251-2.

DOI:10.1007/s12672-025-03251-2

PMID:40739043

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12311089/

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.

摘要

背景

在小细胞肺癌（SCLC）中，氧化应激会破坏氧化还原平衡，并通过DNA损伤、炎症和肿瘤发生促进肿瘤进展和治疗抵抗。谷胱甘肽（GSH）和半胱氨酸（CyS）等硫醇化合物及其氧化形式（GSSG和CySS）可作为氧化应激的标志物。本研究的目的是调查化疗期间GSH/GSSG和CyS/CySS比值的变化，并评估它们作为SCLC预后指标的潜力。

材料与方法

在这项纵向研究中，对60例接受顺铂-依托泊苷化疗的III/IV期SCLC患者的氧化还原生物标志物（GSH/GSSG和CyS/CySS比值）进行了研究。在化疗前、两个周期后和四个周期后采集血浆样本，并通过液相色谱-串联质谱法进行分析。

结果

化疗期间观察到显著的氧化还原变化。两个周期后GSH/GSSG比值降低（p = 0.029），四个周期后升高（p = 0.002）。CyS/CySS动态变化也观察到相同趋势（分别为p = 0.031和p = 0.030）。存活者显示氧化还原平衡恢复，而死亡患者的比值持续较低。Kaplan-Meier分析表明，治疗前较高的GSH/GSSG比值（p = 0.037）预示着更好的生存。发现GSH/GSSG和CyS/CySS比值之间存在正相关（ρ = 0.306，p = 0.019）。