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DNA damage measured in blood cells predicts overall and progression-free survival in germ cell tumour patients.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 1.9 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.mrgentox.2020.503200
Zuzana Sestakova 1 , Katarina Kalavska 2 , Bozena Smolkova 3 , Vera Miskovska 4 , Katarina Rejlekova 5 , Zuzana Sycova-Mila 5 , Patrik Palacka 5 , Jana Obertova 5 , Andrea Holickova 1 , Lenka Hurbanova 1 , Dana Jurkovicova 1 , Jan Roska 1 , Eduard Goffa 1 , Daniela Svetlovska 6 , Michal Chovanec 7 , Jozef Mardiak 7 , Michal Mego 8 , Miroslav Chovanec 1
Affiliation  

Germ cell tumour (GCT) patients who fail to respond to chemotherapy or who relapse have a poor prognosis. Timely and accurately stratifying such patients could optimise their therapy. We identified endogenous DNA damage levels as a prognostic marker for progression-free (PFS) and overall (OS) survival in chemotherapy-naïve GCT patients. In the present study, we have extended our previous results and reviewed the prognostic power of DNA damage level in GCTs. Endogenous DNA damage levels were measured with the comet assay. Receiver operator characteristic analysis was applied to determine the optimal cut-off value and to evaluate its prognostic accuracy. PFS and OS were estimated by the Kaplan-Meier method and compared using the log-rank test. Hazard ratio (HR) estimates were calculated by Cox regression analysis. A cut-off value of 6.34 provided the highest sensitivity and specificity, with area under curve values of 0.813 and 0.814 for disease progression and mortality, respectively. A % DNA in tail > 6.34 was significantly associated with shorter PFS (HR = 9.54, 95 % confidence interval [CI]: 3.43−26.55, p < 0.001) and OS (HR = 14.62, 95 % CI: 3.14−67.95, p = 0.001) by univariate analysis. The prognostic value of DNA damage measurement was confirmed by multivariate models (HR = 6.45, 95 % CI: 2.22−18.75, p = 0.001 for PFS and HR = 9.40, 95 % CI: 1.70−52.09, p = 0.010 for OS), when HR was adjusted for relevant clinical categories. The added prognostic value of DNA damage in combination with International Germ Cell Cancer Collaborative Group (IGCCCG) risk groups has been revealed. Endogenous DNA damage is an independent prognosticator for PFS and OS in GCT patients and its clinical use, particularly in combination with IGCCCG risk groups, may help in stratifying these patients.



中文翻译:

在血细胞中测量的 DNA 损伤可预测生殖细胞肿瘤患者的总体生存和无进展生存。

对化疗无反应或复发的生殖细胞肿瘤 (GCT) 患者预后较差。及时准确地对此类患者进行分层可以优化他们的治疗。我们将内源性 DNA 损伤水平确定为未接受化疗的 GCT 患者的无进展 (PFS) 和总体 (OS) 生存率的预后标志物。在本研究中,我们扩展了之前的结果并回顾了 GCT 中 DNA 损伤水平的预后能力。用彗星试验测量内源性 DNA 损伤水平。接受者操作特征分析用于确定最佳截止值并评估其预后准确性。PFS 和 OS 通过 Kaplan-Meier 方法估计,并使用对数秩检验进行比较。通过 Cox 回归分析计算危险比 (HR) 估计值。截止值为 6。34 提供了最高的敏感性和特异性,疾病进展和死亡率的曲线下面积值分别为 0.813 和 0.814。尾部 DNA 百分比 > 6.34 与较短的 PFS 显着相关(HR = 9.54,95 % 置信区间 [CI]:3.43-26.55,p  < 0.001) 和 OS (HR = 14.62, 95% CI: 3.14−67.95, p  = 0.001) 通过单变量分析。DNA 损伤测量的预后价值由多变量模型证实(HR = 6.45, 95 % CI: 2.22−18.75, p  = 0.001 for PFS and HR = 9.40, 95% CI: 1.70−52.09, p  = 0.010 for OS),当 HR 针对相关临床类别进行调整时。已经揭示了 DNA 损伤与国际生殖细胞癌症协作组 (IGCCCG) 风险组相结合的附加预后价值。内源性 DNA 损伤是 GCT 患者 PFS 和 OS 的独立预后因素,其临床应用,特别是与 IGCCCG 风险组相结合,可能有助于对这些患者进行分层。

更新日期:2020-05-23
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