Orfanakos Kyriakos, Alifieris Constantinos E, Verigos Emmanouil K, Deligiorgi Maria V, Verigos Kosmas E, Panayiotidis Mihalis I, Nikolaou Michail, Trafalis Dimitrios T
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.
Biomedicines. 2024 Jan 9;12(1):134. doi: 10.3390/biomedicines12010134.
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.
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。