鼻咽癌患者血浆游离EBV/DNA的定量检测及其临床意义

Clinical Significance of the Quantitative Analysis of Plasma Epstein-Barr virus DNA Concentration in Nasopharyngeal Carcinoma

目的:探讨血浆EBV/DNA定量分析,在鼻咽癌早期诊断、临床分期、预后判断和监测放疗后转移复发中的临床意义。方法:采用荧光定量PCR方法定量检测经病理确诊为鼻咽癌的120例初治、90例放疗后随诊患者,其中包括60例放疗后持续缓解,30例远处转移和局部复发患者的血浆EBV/DNA含量。结果:初治、远处转移和局部复发的鼻咽癌患者血浆中游离的EBV/DNA检出率分别为96.0%、95.0%和100%,显著高于治疗后持续缓解鼻咽癌患者、健康对照者和非鼻咽癌的肿瘤患者;初治鼻咽癌患者各TNM分期之间血浆EBV/DNA拷贝数有显著统计学差异,晚期患者(Ⅲ+Ⅳ)期血浆EBV/DNA中位拷贝数显著高于早期患者(Ⅰ+Ⅱ)期;初治患者治疗后已出现局部和远处转移者,治疗前血浆EBV/DNA中位数显著高于尚未出现复发转移患者;初治患者治疗前血浆EBV/DNA≥40000拷贝/ml与<40000拷贝/ml两个水平,患者22个月无复发生存率分别为46.1%和92.9%,有显著统计学差异;放疗后复发、转移鼻咽癌患者血浆EBV/DNA的中位拷贝数显著高于治疗后持续缓解患者。结论:采用荧光定量PCR方法检测鼻咽癌患者血浆中游离的EBV/DNA是一种敏感可靠的方法,对于鼻咽癌早期诊断、鉴别诊断、分期、判断预后、监测治疗后复发和远处转移具有重要的临床意义,有可能成为鼻咽癌的血清肿瘤标记物。

Objective: To quantitative detect plasma EBV/DNA level and its application in early diagnosis, clinical staging, prediction prognostication and monitoring recurrence and metastasis in nasopharyngeal carcinoma. Methods: Using Fluorescent quantitative PCR , the content of plasma EBV/DNA were detected in 120 patients with primary NPC, 90 patients with follow up including 60 in clinical remission and 30 with distant metastasis and local recurrence. Results: Plasma EBV/DNA was detectable in 96% (115/120) of primary NPC, 95% (21/22) of NPC with distant metastasis, and 100% (8/8) of recurrent NPC, the detectable proportion in these groups was significantly higher than that in control subjects. In primary NPC patients, patients in advanced TNM stage had significant higher plasma EBV/DNA concentration than those of in early TNM stage; The plasma EBV/DNA concentration of patients had local recurrence and/or distant metastasis after treatment were significant higher than those with no evidence of local recurrence and/or distant metastasis, 2 year disease free survival rate were significant lower in patients with plasma EBV/DNA concentration more than 40 000copies/ml comparedwith those with less than 40 000copies/ml (46.1% vs 92.9%). For those follow-up patients after treatment, the detectable proportion and concentration in recurrent and metastatic NPC patients were significantly higher than that of in clinical remissive NPC patients. Conclusions: Our results suggest that the quantum of plasma EBV-DNA is a sensitive, valuable and reliable tumor marker for reinforcing clinical diagnosing, staging, prediction prognostication of early treatment failure as well as monitoring of metastasis and recurrence in endemic area NPC patients.