Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset-FISABIO, 46017 Valencia, Spain.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontotología-INCLIVA, Universidad de Valencia, 46010 Valencia, Spain.
Int J Mol Sci. 2021 Jun 8;22(12):6183. doi: 10.3390/ijms22126183.
The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.
氧化应激（OS）在癌症中的作用是一个备受关注的问题，因为活性氧（ROS）及其氧化产物在肿瘤发生、进展和转移扩散的起始中具有重要意义。人们已经做出了巨大的努力来确定 ROS 诱导的致癌机制；然而，OS 副产物作为潜在的肿瘤标志物（TMs）的验证仍有待建立。这项干预性研究共包括 80 名结直肠癌（CRC）患者和 60 名对照。通过测量 CRC 患者血清中还原型谷胱甘肽（GSH）、其氧化形式（GSSG）和谷胱甘肽氧化还原状态（以 GSSG/GSH 比值表示），我们发现与健康受试者相比存在显著变化。这些发现与谷胱甘肽作为 TM 的有效性一致。CRC 组的巯基氧化还原状态显著向氧化方向增加，并与肿瘤状态和临床演变显著相关。血清谷胱甘肽水平的敏感性和特异性远高于经典 TM CEA 和 CA19.9。我们得出结论，GSSG/GSH 比值是一种简单的检测方法，可以作为一种新的临床 TM 来诊断和监测 CRC。
