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8-羟基脱氧鸟苷(8-OHdG)血清浓度对接受放疗的非小细胞肺癌(NSCLC)患者的预测价值

The Predictive Value of 8-Hydroxy-Deoxyguanosine (8-OHdG) Serum Concentrations in Irradiated Non-Small Cell Lung Carcinoma (NSCLC) Patients.

作者信息

Orfanakos Kyriakos, Alifieris Constantinos E, Verigos Emmanouil K, Deligiorgi Maria V, Verigos Kosmas E, Panayiotidis Mihalis I, Nikolaou Michail, Trafalis Dimitrios T

机构信息

Laboratory of Pharmacology, Faculty of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Department of Radiation Therapy, 401 General Military Hospital, 11525 Athens, Greece.

出版信息

Biomedicines. 2024 Jan 9;12(1):134. doi: 10.3390/biomedicines12010134.

Abstract

Ionizing radiation is strongly linked to direct or indirect DNA damage, as with the production of reactive oxygen species (ROS), which in turn produce DNA damage products, such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In this study, we aimed to investigate the formation of 8-OHdG after irradiation in patients with non-small cell cancer (NSCLC) and its use as a biomarker. Sixteen patients with squamous and thirty-six patients with non-squamous pathology were included. An enzyme-linked-immunosorbent assay (ELISA) was performed before and after radiation. A dose-dependent relationship was confirmed: 8-OHdG plasma concentrations, increased in the total of NSCLC patients and specifically with a linear correlation in non-squamous pathology; in squamous histology, after an initial increase, a significant decrease followed after 20 Gy dose of irradiation. The pretreatment total irradiated tumor volume (cm) was positively correlated with 8-OHdG levels in patients with squamous histology. When plotting the 8-OHdG plasma concentration at a 10 Gy irradiation dose to the baseline, the AUC was 0.873 (95% CI 0.614-0.984), < 0.0001, with an associated criterion value of >1378 as a cutoff (sensitivity 72.7%, specificity 100%). When normalizing this ratio to BSA, the associated criterion cutoff value was >708 (sensitivity of 100%, specificity 80%). Lastly, 8-OHdG levels were closely related with the development of radiation-induced toxicities.

摘要

电离辐射与直接或间接的DNA损伤密切相关,例如活性氧(ROS)的产生,而活性氧又会产生DNA损伤产物,如8-羟基-2'-脱氧鸟苷(8-OHdG)。在本研究中,我们旨在调查非小细胞癌(NSCLC)患者放疗后8-OHdG的形成情况及其作为生物标志物的用途。纳入了16例鳞状病理患者和36例非鳞状病理患者。在放疗前后进行了酶联免疫吸附测定(ELISA)。证实了剂量依赖性关系:NSCLC患者总体的8-OHdG血浆浓度升高,特别是在非鳞状病理中呈线性相关;在鳞状组织学中,在初始升高后,20 Gy照射剂量后显著下降。鳞状组织学患者的预处理总照射肿瘤体积(cm)与8-OHdG水平呈正相关。将10 Gy照射剂量下的8-OHdG血浆浓度与基线进行绘图时,曲线下面积(AUC)为0.873(95%可信区间0.614-0.984),P<0.0001,相关标准值>1378作为截断值(敏感性72.7%,特异性100%)。将该比值标准化为牛血清白蛋白(BSA)时,相关标准截断值>708(敏感性100%,特异性80%)。最后,8-OHdG水平与放射性毒性的发生密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cad/10813052/e9e9e77f9e73/biomedicines-12-00134-g001.jpg

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