Quantitative analysis of the transrenal excretion of circulating EBV DNA in nasopharyngeal carcinoma patients
Quantitative analysis of the transrenal excretion of circulating EBV DNA in nasopharyngeal carcinoma patients
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DOI：
10.1158/1078-0432.ccr-08-1112
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发表时间：
2008-08-01
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 F.;Lo, Y. M. Dennis
目的：循环无细胞DNA的经肾清除存在争议。在这项研究中，我们使用NPC作为一个模型，以调查是否循环EBV DNA可以排泄到尿液中，并量化的贡献，肾脏排泄的清除血浆EBV DNA.Experimental Design：尿EBV DNA的定量分析74例NPC患者使用实时PCR与两种不同的扩增子大小。尿中EB病毒DNA的浓度表示为每毫摩尔肌酐的拷贝数（拷贝数/mmol Cr），以尽量减少水化状态的个体间差异的影响。结果：使用59 bp的实时PCR检测56%的NPC患者的尿中可检测到EB病毒DNA。通过59-和76-bp测定法测量的尿EBV DNA浓度中位数分别为7，040和290拷贝/mmol Cr。尿中可检测到EBV DNA的患者血浆浓度明显较高，血浆和尿液中EBV DNA浓度呈正相关。血浆中EBVDNA经尿排泄率为肌酐排泄率的0.0026%。结论：鼻咽癌患者循环中EBVDNA可经肾排泄入尿，其排泄率与DNA分子大小呈负相关。由于血浆和尿液EBV DNA浓度之间存在正相关性，因此尿液EBV DNA分析可能适用于NPC患者的监测和诊断的超无创检测。
Purpose:The existence of transrenal clearance of circulating cell-free DNA is controversial. In this study, we used NPC as a model to investigate if circulating EBV DNA can be excreted into urine and to quantify the contribution of renal excretion to the clearance of plasma EBV DNA.Experimental Design: Quantitative analysis of urine EBV DNA was done for 74 NPC patients using real-time PCR with two different amplicon sizes. The urine concentration of EBV DNA was expressed as copies per millimole of creatinine (copies/mmol Cr) to minimize the effects of interindividual variations in hydration status.Results: EBV DNA was detectable in the urine of 56% NPC patients using a 59-bp real-time PCR assay. The median urine EBV DNA concentrations measured by the 59- and 76-bp assays were 7,040 and 290 copies/mmol Cr, respectively. Patients with detectable urine EBV DNA had significantly higher plasma concentrations, with a positive correlation between the plasma and urine concentrations of EBV DNA. The fraction of plasma EBV DNA excreted into the urine was 0.0026% of that for creatinine.Conclusions: We have shown that circulating EBV DNA can be excreted transrenally into urine in NPC patient and the fraction of excretion is negatively associated with the size of the DNA molecules. Because there is a positive correlation between plasma and urine EBV DNA concentration, urine EBV DNA analysis may potentially be applicable as an ultra-noninvasive test for the monitoring and prognostication of NPC patients.