血浆 EB病毒游离 DNA检测对监测鼻咽癌患者预后的意义

背景与目的:有报道 , 测定血浆中的 EB病毒游离 DNA( EBV-DNA)的拷贝数可作为诊断及监测鼻咽癌患者病情变化的手段之一.本研究旨在评价血浆 EBV-DNA检测在鼻咽癌患者预后监测上的价值, 并进一步与 VCA/IgA、 EA/IgA进行比较.方法:比较鼻咽癌放疗后 30例远处转移患者、 22例局部复发患者、 24例无 瘤生存者血浆中 EBV-DNA、 VCA/IgA、 EA/IgA水平.分别应用荧光定量 PCR方法检测血浆 EBV-DNA水平,免疫酶法检测 VCA/IgA、 EA/IgA;前瞻性观察 20例初诊鼻咽癌患者放疗前、放疗剂量达 40 Gy时及放疗结束时上述指标的变化. 结果:放疗后各组不同预后患者的血浆 EBV-DNA含量的中位数有显著性差异, 远处转移组为 135 100 copies/ml(四分线区域 5 525～ 1 003 750 copies/ml) >局部复发组的 20 500(四分线区域 0～ 58 500 copies/ml) > 无瘤生存组的 0 copy/ml(四分线区域 0～ 0 copy/ml), P均 < 0.05. 远处转移组的血浆 EBV-DNA水平高者较多, 当阳性标准为 1 000 000 copies/ml时,诊断远处转移组的敏感性为 27.3%,而诊断局部复发组的敏感性为 0.0%,特异性均为 100.0%.在初诊患者放疗前、放疗剂量达 40 Gy时及放疗结束时, EBV-DNA水平逐渐降低,平均含量分别为 32 050 copies/ml(四分线区域 3 880～ 317 750 copies/ml)、 0 copy/ml(四分线区域 0～ 14 375 copies/ml)、 0 copy/ml(四分线区域 0～ 2 940 copies/ml), P均 < 0.05, 而 VCA/IgA、 EA/IgA的水平未见明显变化. 结论: 血浆 EBV-DNA检测可用于监测鼻咽癌患者预后,其价值明显优于 VCA/IgA、 EA/IgA.

Significance of cell-free Epstein-Barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma

BACKGROUND &OBJECTIVE:It has been reported that cell free Epstein Barr virus (EBV DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV DNA in monitoring the prognosis of nasopharyngeal carcinoma and to compare with VCA/IgA and EA/IgA. METHODS: EBV DNA, VCA/IgA,and EA/IgA levels in plasma were detected in different NPC patients after radiotherapy, including 30 distant metastasis patients, 22 locoregional recurrence patients, 24 remission individuals who had been followed up more than 2 years after treatment. EBV DNA was detected using real time quantitative PCR system;VCA/IgA and EA/IgA were tested using regular immunofluorescence. In cohort study, the indexes were tested in different radiation periods for the 20 new cases of nasopharyngeal carcinoma. RESULTS: The median plasma EBV DNA concentration was 135,100 copies/ml (interquartile range: 5,525-1,003,750) in metastasis group, 20,500 copies/ml (interquartile range: 0-58,500) in locoregional recurrence group and 0 copies/ml (interquartile range: 0-0) in continuous remission group (P< 0.05). The levels of VCA/IgA and EA/IgA had no significant difference in different groups. The high level of EBV DNA concentration in metastasis group was more than that in locoregional recurrence group. At the level of 1 000 000 copies/ml, EBV DNA indicated distant metastasis of NPC with a specificity of 100%and a sensitivity of 27.3%; however, the sensitivity was 0 copies/ml in locoregional recurrence group. For the 20 new patients, EBV DNA concentration gradually decreased in the radiation period, 32,050 copies/ml (interquartile range: 3,880-317,750) before radiation, 0 copies/ml (interquartile range: 0-14,375) when 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) when the radiation finished (P< 0.05). However, the levels of VCA/IgA and EA/IgA had no significant difference. CONCLUSION: The plasma cell free EBV DNA is more valuable than VCA/IgA and EA/IgA for monitoring the prognosis of NPC patients.