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异柠檬酸脱氢酶1(IDH1)野生型胶质母细胞瘤患者的尿8-羟基-2'-脱氧鸟苷水平升高,且与胶质瘤的肿瘤复发相关。

Urinary 8-hydroxy-2'-deoxyguanosine levels are elevated in patients with IDH1-wildtype glioblastoma and are associated with tumor recurrence in gliomas.

作者信息

Tuna Gamze, Bekar Nazlı Ecem Dal, İşlekel Sertaç, İşlekel Gül Hüray

机构信息

Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.

Department of Medical Biochemistry, Faculty of Medicine, Izmir University of Economics, Izmir, Turkey.

出版信息

DNA Repair (Amst). 2023 Apr;124:103463. doi: 10.1016/j.dnarep.2023.103463. Epub 2023 Feb 16.

DOI:10.1016/j.dnarep.2023.103463
PMID:36841018
Abstract

2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification includes molecular diagnostic parameters such as isocitrate dehydrogenase (IDH) mutation or 1p19q codeletion status, in addition to the classical histological classification. Several studies have revealed that patients with IDH1 mutation have a longer survival rate compared to wildtype individuals. In glioma cells, increased oxidative stress has been identified. However, till now, the relation between oxidative stress levels and IDH1 mutation status in those patients was not examined. Therefore, the aim of this study was to investigate the urinary levels of oxidatively induced DNA damage products, 8-hydroxy-2'- deoxyguanosine (8-OH-dG), (5'R) and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA) as reliable oxidative stress markers in patients with IDH1-wildtype (n = 20) and IDH1-mutant (n = 22) glioma. Absolute quantification of 8-OH-dG, R-cdA and S-cdA was achieved by liquid chromatography-tandem mass spectrometry with isotope dilution. The levels of 8-OH-dG were significantly greater in IDH1-wildtype glioma patients than those in IDH1-mutant ones (p = 0.017). No statistically significant difference was observed for R-cdA and S-cdA levels. 8-OH-dG levels were positively correlated with patients' tumor recurrence in all patients (r = 0.382, p = 0.014). The mutation status of glioma is well correlated with oxidative stress. Examination of noninvasively measured oxidative DNA damage products along with IDH1 mutation status in glioma patients, might be particularly important in terms of evaluating and monitoring the effectiveness of treatment.

摘要

2021年世界卫生组织(WHO)中枢神经系统(CNS)肿瘤分类除了经典的组织学分类外,还纳入了分子诊断参数,如异柠檬酸脱氢酶(IDH)突变或1p19q共缺失状态。多项研究表明,与野生型个体相比,IDH1突变患者的生存率更长。在胶质瘤细胞中,已发现氧化应激增加。然而,迄今为止,尚未研究这些患者氧化应激水平与IDH1突变状态之间的关系。因此,本研究的目的是调查IDH1野生型(n = 20)和IDH1突变型(n = 22)胶质瘤患者尿液中氧化诱导的DNA损伤产物8-羟基-2'-脱氧鸟苷(8-OH-dG)、(5'R)和(5'S)-8,5'-环-2'-脱氧腺苷(R-cdA和S-cdA)的水平,作为可靠的氧化应激标志物。采用同位素稀释液相色谱-串联质谱法对8-OH-dG、R-cdA和S-cdA进行绝对定量。IDH1野生型胶质瘤患者的8-OH-dG水平显著高于IDH1突变型患者(p = 0.017)。R-cdA和S-cdA水平未观察到统计学显著差异。在所有患者中,8-OH-dG水平与患者肿瘤复发呈正相关(r = 0.382,p = 0.014)。胶质瘤的突变状态与氧化应激密切相关。在胶质瘤患者中,检测非侵入性测量的氧化DNA损伤产物以及IDH1突变状态,对于评估和监测治疗效果可能尤为重要。

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