单个核细胞EB病毒DNA载量在鼻咽癌患者中的变化初探

Preliminary study on the change of Epstein-Barr virus DNA load in patients with nasopharyngeal carcinoma

目的探讨外周血单个核细胞EB病毒DNA(Epstein-Barr virus DNA,EB-DNA)在鼻咽癌患者诊疗中的变化和临床意义。方法选择2014年4月至2017年10月期间,在中国科技大学附属第一医院西区门诊和住院部初诊经病理学确诊为鼻咽癌(nasopharyngeal carcinoma,NPC)患者220例,年龄12～80岁,按≤30岁～≥71岁的每10岁间隔分为6组,用实时荧光定量聚合酶链反应检测外周血单个核细胞中EB-DNA载量在NPC患者不同性别、年龄、病理类型、临床分期的阳性率和载量的差异;对接受放化疗治疗前后的82例NPC患者的EB-DNA载量变化连续定期随访2年以上,以分析评价其变化与NPC患者复发与转移的关系。结果 220例NPC患者外周血单个核细胞EB-DNA阳性率为41.4%(91/220例),EB-DNA载量为0.0(0.0～612.5)拷贝/ml,但EB-DNA阳性率和载量在不同性别[男42%,女40%;男0.0(0.0～568.0)拷贝/ml,女0.0(0.0～899.5)拷贝/ml]、病理类型患者间的差异均无统计学意义(χ~2=0.079,Z=-0.106;χ~2=0.024,Z=-1.182;P均>0.05),但EB-DNA阳性率随年龄增长(≤30岁～≥71岁的6个年龄组阳性率分别为23.1%、47.1%、38.6%、36.8%、52.9%、63.6%)和临床分期(TNM分期Ⅱ+Ⅲ期27.4%、Ⅳa期45.7%、Ⅳb期75.0%)不断增高(χ~2=3.683,P=0.031;χ~2=16.996,P<0.001)。82例随访NPC患者治疗后有57例EB-DNA载量中位数明显低于治疗前[前1390.0(550.0～6535.0)拷贝/ml,后0.0(0.0～0.0)拷贝/ml;Z=-5.997,P<0.001],有25例患者治疗后EB-DNA载量[1490.0(348.5～3965.0)拷贝/ml]高于治疗前[0.0(0.0～205.0)拷贝/ml,Z=-4.529,P<0.001],且两组治疗后EB-DNA载量差异有统计学意义(Z=-6.911,P<0.001),治疗后EB-DNA载量升高的25例NPC患者中有18例发生局部复发或远处转移。结论 NPC患者外周血单个核细胞中EB-DNA载量阳性率随着年龄增长和临床分期的上升不断增高,治疗后定期监测患者EB-DNA载量变化对其预后有一定临床应用价值。

Objective To investigate the changes and clinical significance of Epstein-Barr virus DNA(EB-DNA) in peripheral blood mononuclear cells in patients with nasopharyngeal carcinoma. Methods Two hundred and twenty cases of nasopharyngeal carcinoma (NPC) diagnosed by pathology at the out-patient and inpatient department of the First Affiliated Hospital of University of Science and Technology of China during April 2014 and October 2017 were enrolled in this study. These patients were aged between 12 and 80 and were divided into 6 groups according to the interval of 10 years of age between ≥ 71 and ≤ 30 years of age. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to quantify the EB-DNA loads in peripheral blood mononuclear cells of patients with nasopharyngeal carcinoma. Correlation between EB-DNA load and clinicopathological parameters including gender, age, pathological type and clinical stage was studied. The EB-DNA loads in 82 patients with NPC before and after radiotherapy were followed up for more than 2 years in order to evaluate the relationship between the EB-DNA load change and the recurrence and metastasis of the patients with NPC. Results The positive rate of EB-DNA in peripheral blood mononuclear cells in 220 cases of nasopharyngeal carcinoma was 41.4%(91/220);and the average EB-DNA load was 0.0(0.0~612.5) copies/ml. The positive rates and EB-DNA loads had no significant difference between male and female [42% vs. 40%;0.0(0.0-568.0) copies/ ml vs. 0.0(0.0-899.5) copies/ml] and pathological types (χ^2=0.079, Z=-0.106;χ^2=0.024, Z=-1.182;P > 0.05). The positive rate of EB-DNA increased with age (the positive rates of EB-DNA in the 6 groups were 23.1%, 47.1%, 38.6%, 36.8%, 52.9% and 63.6%, respectively) and clinical stage (27.4% in TNM stage II + III, 45.7% in IV a, and 75.0% in IV b,χ^2=3.683,P=0.031;χ^2=16.996,P < 0.001). In 82 cases of NPC, EB-DNA loads in 57 patients were significantly lower than that before treatment [0.0(0.0~0.0) copies/ml vs. 1390.0(550.0~6535.0) copies/ml;Z=-5.997,P < 0.001]. However, in the other 25 patients, the EB-DNA loads were higher than that before treatment [1490.0(348.5~3965.0) copies/ml vs. 0.0(0.0~205.0) copies/ml, Z=-4.529,P < 0.001] and significantly difference of EB-DNA loads between the two groups after treatment were found (Z=-6.911, P < 0.001). Eighteen of the 25 patients had local recurrence or distant metastasis after treatment. Conclusions The positive rate of EB-DNA in peripheral blood mononuclear cells of patients with nasopharyngeal carcinoma increased with age and clinical stage. Regular monitoring of EB-DNA loads after treatment has certain clinical value for prognosis.