Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients
Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients
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DOI：
10.1158/1078-0432.ccr-08-0182
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发表时间：
2008-07-01
影响因子：
11.5
通讯作者：
Lo, Y. M. Dennis
中科院分区：
文献类型：
--
作者：
Chan, K. C. Allen;Leung, Sing-Fai;Lo, Y. M. Dennis
目的：在癌症患者中观察到循环核酸完整性的异常。然而，这种变化的临床意义尚未完全阐明。在本研究中，我们调查了鼻咽癌 (NPC) 患者的血浆 DNA 完整性及其与放疗后患者生存率的关系。实验设计：对 105 名鼻咽癌患者在治疗性放疗前后以及 40 名健康对照者的血浆 DNA 完整性进行了分析。通过两次针对瘦素基因的实时 PCR 测量每个样本的血浆 DNA 浓度。两次检测的扩增子大小分别为 105 和 201 bp。完整性指数计算为两个浓度的比率（201 bp/105 bp）。完整的循环DNA越多，完整性指数越高。结果：鼻咽癌患者的血浆DNA完整性指数显着高于健康对照（中位数，0.356 vs 0.238；P < 0.001）。放疗后，70% 的鼻咽癌患者血浆 DNA 完整性指数下降。治疗后血浆DNA完整性持续异常的患者比DNA完整性降低的患者的生存概率显着降低（P < 0.001，Kaplan-Meier）。结论：NPC与循环游离DNA完整性紊乱相关。放射治疗后 DNA 完整性畸变的持续存在与无病生存概率的降低有关。因此，血浆DNA完整性的测量可以作为检测和监测恶性疾病的有用标记。
Purpose: Aberrations of circulating nucleic acid integrity have been observed in cancer patients. However, the clinical significance of such changes has not been completely elucidated. In this study, we investigated the plasma DNA integrity in nasopharyngeal carcinoma (NPC) patients and its association with patients' survival after radiotherapy.Experimental Design: Plasma DNA integrity was analyzed for 105 NPC patients before and after curative-intent radiotherapy and for 40 healthy controls. The plasma DNA concentration of each sample was measured by two real-time PCRs targeting the leptin gene. The amplicon sizes of the two assays were 105 and 201 bp. The integrity index was calculated as the ratio of the two concentrations (201 bp/105 bp). More intact circulating DNA would give a higher integrity index.Results: The plasma DNA integrity index of the NPC patients was significantly higher than that of the healthy controls (median, 0.356 versus 0.238; P < 0.001). After radiotherapy, a reduction in plasma DNA integrity index was observed in 70% NPC patients. Patients with persistent aberrations of plasma DNA integrity had significantly poorer survival probability than those with reduced DNA integrity after treatment (P < 0.001, Kaplan-Meier).Conclusions: NPC is associated with disturbances in the integrity of circulating cell-free DNA. The persistence of DNA integrity aberrations after radiotherapy is associated with reduced probability of disease-free survival. Therefore, the measurement of plasma DNA integrity may serve as a useful marker for the detection and monitoring of malignant diseases.