Prognostic value of plasma Epstein-Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

Plasma Epstein-Barr virus DNA as a biomarker for nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC)is common in southern China and Southeast Asia.Epstein-Barr virus(EBV)infection is an important etiology for NPC,and EBV genome can be detected in almost all tumor tissues of NPC in this region.Plasma EBV DNA,when quantitatively analyzed using real-time polymerase chain reaction(PCR),has been developed as a biomarker for NPC.In this review,the different clinical applications of plasma EBV DNA in the management of NPC,including screening,monitoring,and prognostication,are discussed.In addition,the biological issues of circulating EBV DNA,including the molecular nature and clearance kinetics,are also explored.

Differential DNA methylation profiles of human B lymphocytes and Epstein-Barr virus-immortalized B lymphocytes

Objective： This study aimed to comprehensively assess Epstein-Barr virus（EBV）-induced methylation alterations of B cell across whole genome.Methods： We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines（LCLs） from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results： DNA methylation analysis revealed 87,732 differentially methylated Cp G sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated Cp G sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in Cp G islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore（N_shore and S_shore）. Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions： Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.

血浆EBV-DNA联合窄带成像技术在鼻咽癌复发监测中的应用价值

目的探讨血浆EB病毒DNA(EBV-DNA)联合窄带成像技术(NBI)在鼻咽癌(NPC)复发监测中的应用价值。方法选取NPC复发患者86例和未复发患者142例为研究对象,观察EBVDNA、NBI、EBV-DNA联合NBI方法在NPC复发诊断中的灵敏度、特异度、阳性预测值、阴性预测值、一致性检验(Kappa值);采用受试者工作特征曲线(ROC)分析EBV-DNA、NBI、EBV-DNA联合NBI诊断NPC复发的曲线下面积(AUC)。结果ROC分析结果显示,EBV-DNA、NBI、EBV-DNA联合NBI诊断NPC复发的AUC分别为0.826、0.845、0.893,EBV-DNA联合NBI预测复发的AUC比单一方法检测大,差异具有统计学意义(P<0.05)。分层分析结果显示,预测早期患者NPC复发和晚期NPC复发的AUC为0.924和0.865,Kappa值为0.827和0.696。结论在监测NPC复发诊断中,EBV-DNA联合NBI方法比单一方法效能高,在临床分期为早期的NPC患者中效果更佳,值得临床上应用推广。

Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

Serological tests for antibodies specific for Epstein-Barr virus(EBV) antigens are frequently used to define infection status and for the differential diagnosis of other pathogens responsible for mononucleosis syndrome. Using only three parameters [viral capsid antigen(VCA) Ig G, VCA Ig M and EBV nuclear antigen(EBNA)-1 Ig G],it is normally possible to distinguish acute from past infection: the presence of VCA Ig M and VCA Ig G without EBNA-1 Ig G indicates acute infection, whereas the presence of VCA Ig G and EBNA-1 Ig G without VCA Ig M is typical of past infection. However, serological findings may sometimes be difficult to interpret as VCA Ig G can be present without VCA Ig M or EBNA-1 Ig G in cases of acute or past infection, or all the three parameters may be detected simultaneously in the case of recent infection or during the course of reactivation. A profile of isolated EBNA-1 Ig G may also create some doubts. In order to interpret these patterns correctly, it is necessary to determine Ig G avidity, identify anti-EBV Ig G and Ig M antibodies by immunoblotting, and look for heterophile antibodies, anti-EA(D) antibodies or viral genome using molecular biology methods. These tests make it possible to define the status of the infection and solve any problems that may arise in routine laboratory practice.

Oncogenic induction of cellular high CpG methylation by Epstein-Barr Barr virus in malignant epithelial cells

Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.

Epstein-Barr病毒DNA多聚酶基因扩增和表达载体构建

【目的】扩增Epstein Barr病毒 (EBV)DNA多聚酶基因 ,构建高效表达载体。【方法】根据EBV全基因序列 ,在EBVDNA多聚酶基因的 3′、5′端设计一对附加EcoRⅠ和HindⅢ酶切位点的特异性引物 ,以B95 8细胞DNA为模板 ,采用改良PCR方法扩增出EBVDNA多聚酶基因 (3 0 44bp)。用EcoRⅠ和HindⅢ酶切该基因片断并克隆至表达载体 pMAL p2 ,采用蓝白斑试验筛选阳性菌落。EcoRⅠ和HindⅢ酶切分析、鉴定重组体 pEBP。【结果】通过电泳鉴定 ,PCR产物为 3 0 44bp ,与EBVDNA多聚酶基因大小一致。经蓝白斑试验及限制性DNA内切酶分析 ,成功地筛选到EBVDNA多聚酶基因重组表达质粒 pEBP。【结论】本实验成功地扩增出完整EBVDNA多聚酶基因 ,并构建了高效表达重组体 ,为进一步在体外表达、制备EBVDNA多聚酶蛋白奠定了基础。

Epstein-Barr病毒DNA在鼻咽癌临床应用中的进展

鼻咽癌是我国南部地区常见的恶性肿瘤,目前临床上仍以TNM分期为主进行治疗方案的选择和预后判断。随着生物学标记物的深入研究,尤其是针对EB病毒DNA(Epstein-Barr virus DNA,EBV-DNA)众多研究的出现,EBV-DNA在鼻咽癌诊断和疗效预测等方面显示出良好的特异性和敏感度,可以成为鼻咽癌重要的筛查工具,也可监测治疗后残余疾病并提示疾病复发情况,还可以作为TNM分期的补充建立新的分期模型指导鼻咽癌患者的临床治疗。EBV-DNA的临床应用可使未来无症状及治疗效果不佳的鼻咽癌患者较早被发现,并且使治疗过程更加精准化。

Epstein-Barr病毒特异性酶类及其抗体研究的进展

本文介绍我室过去10年对EBV特异性酶类及其抗体的研究进展。主要方向为:①EBV特异性DNase抗体(EDAb)血清流行病学及其在鼻咽癌(NPC)早期发现中的作用。②EDAb测定技术的进展。③NPC组织中的EBV-DNase及EBV-DNA多聚酶的研究。应用情况表明EDAb检测在NPC早期发现中具有较高的灵敏度及特异性。NPC组织中的EBV-DNase及EBV-DNA多聚酶的研究可能对NPC的病毒病因的研究有所助益。

儿童传染性单核细胞增多症临床表现及外周血Th1/Th2型细胞标志物与EB病毒-DNA载量的关系

目的探讨儿童传染性单核细胞增多症(IM)临床表现及外周血Th1/Th2型细胞标志物与EB病毒(EBV)-DNA载量的关系。方法选择2019年12月—2021年5月在苏州市第九人民医院和苏州市吴江区儿童医院就诊的IM患儿,共纳入研究63例,根据患儿的EBV-DNA载量(中位水平),分为高载量组(31例)和低载量组(32例),比较两组患儿的临床特征、T淋巴细胞亚群水平(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、Th1/Th2型细胞标志物(IFN-γ、IL-4)水平及肝功能,并分析EBV-DNA载量与T淋巴细胞亚群水平及Th1/Th2型细胞标志物的相关性。记录患儿住院时间及转归情况。结果高载量与低载量组患儿的发热、咽峡炎、颈部淋巴结肿大、皮疹发生例数比较差异无统计学意义(P>0.05),高载量组患儿的肝脾肿大、眼睑水肿发生率高于低载量组(P<0.05);高载量组患儿的CD3^(+)、CD8^(+)、AST、ALT、IL-4水平均高于低载量组,CD4^(+)、CD4^(+)/CD8^(+)、IFN-γ水平低于低载量组(P<0.05);CD3^(+)、CD8^(+)、IL-4水平与EBV-DNA载量呈正相关(P<0.05),CD4^(+)、CD4^(+)/CD8^(+)、IFN-γ水平与EBV-DNA载量呈负相关(P<0.05);高载量组患儿的住院时间较低载量组长(P<0.05);复诊时发现,高载量组患儿的EBV-DNA载量阳性例数、颈部淋巴结肿大例数均高于低载量组,差异有统计学意义(P<0.05),两组肝脾肿大例数比较,差异无统计学意义(P>0.05)。结论IM患儿多出现发热、咽峡炎和颈部淋巴结肿大等临床症状,EBV-DNA高载量患儿临床症状更严重,免疫功能更紊乱;EBV-DNA载量及Th1/Th2型细胞标志物的检测对IM病情诊断及对病情严重程度了解具有重要意义。

儿童EB病毒DNA与肺炎的相关因素分析

目的:探讨儿童EB病毒(Epstein-Barr virus,EBV)DNA与肺炎的相关因素,提高临床医师对EBV感染儿童诊疗的认识。方法:回顾性选择2021年5月—2023年4月惠州市中心人民医院和惠州市第一妇幼保健院住院的EBV-DNA阳性患儿612例,收集同期住院的EBV-DNA阴性患儿1178例为对照组。根据有无合并肺炎将EBV-DNA阳性患儿分为肺炎组(n=242)及非肺炎组(n=347),采用logistic回归分析探讨儿童EBV-DNA阳性合并肺炎的相关因素。结果:612例EBV-DNA阳性患儿中,男女比例为1.35∶1,发病年龄3个月~13岁,婴儿期21例(3.4%)、幼儿期136例(22.2%)、学龄前期319例(52.1%)、学龄期136例(22.2%),患者高峰年龄为学龄前期。EBV-DNA阳性合并肺炎患儿242例(39.5%),其中15例(2.5%)发展为重症肺炎。EBV-DNA阳性与阴性患儿比较,合并肺炎情况差异有统计学意义(P<0.05)。logistic回归分析显示,相比正常体温,最高体温区间37.3~<38℃的OR值为6.165,肝脏肿大、白细胞计数及补体C3的OR值分别为3.525、0.952、4.605(均P<0.05)。结论:EBV-DNA阳性患儿不同年龄段分布情况不同,最高体温、肝脏肿大、白细胞计数及补体C3为EBV-DNA阳性合并肺炎的相关因素。

EB病毒VCA-IgA抗体及病毒DNA载量在系统性红斑狼疮患者中的表达

目的:检测EB病毒VCA-IgA抗体及病毒DNA载量在系统性红斑狼疮(SLE)患者外周血中的表达,探讨EB病毒与SLE的相关性。方法:分别采用酶联免疫吸附试验(ELISA)法和实时定量PCR方法检测EB病毒VCA-IgA抗体和EB病毒DNA载量。同时分析EB病毒VCA-IgA抗体与SLE患者的实验室指标抗Sm抗体、抗dsDNA抗体、补体C3和C4的相关性。结果:248例SLE患者中,49例EBV-VCA-IgA抗体阳性,167例健康对照者中12例阳性,SLE患者阳性率明显高于健康对照者(19.8%vs7.2%;P<0.001);SLE患者EB病毒载量也明显高于健康对照者。EB病毒VCA-IgA抗体阳性与抗Sm抗体、抗dsDNA抗体、补体C3和C4不相关。结论:EB病毒感染与SLE相关,EB病毒VCA-IgA抗体阳性者有较高的DNA载量,SLE的发病危险性亦高,EB病毒重新活化与SLE活动有关。

血浆EBV DNA水平与EBVCA-IGA抗体滴度对鼻咽癌诊断作用的对比研究

目的比较研究血浆EBV DNA水平与EBVCA-IGA抗体滴度对鼻咽癌的诊断作用。方法73例初治鼻咽癌患者经病理确诊,按福州会议"1992鼻咽癌分期"进行TNM分期,检测患者空腹血浆EBV DNA水平和EBVCA-IGA抗体滴度。采用SPSS13.0统计软件对资料进行比较,结合临床资料对结果进行分析。结果血浆EBV DNA水平与EBVCA-IGA抗体滴度对鼻咽癌的诊断作用比较,差异有统计学意义,血浆EBV DNA的诊断特异性明显高于后者;血浆EBV DNA水平在有、无淋巴结转移组间的比较,差异有统计学意义(P<0.05)。结论与EBVCA-IGA抗体滴度相比,血浆EBV DNA对NPC诊断有较高特异性;血浆EBV DNA水平可能预示鼻咽癌淋巴结转移。

鼻咽癌Epstein－Barr病毒受体（EBVR／CR＿2）基因的病毒结合区的序列测定

Ｅｐｓｔｅｉｎ－Ｂａｒｒ病毒（ＥＢＶ）进入鼻咽上皮细胞的途径，是人们研究ＥＢＶ与鼻咽癌（ＮＰＣ）的病因关系时所必须回答的一个问题。用抗ＥＢＶ受体（ＥＢＶＲ／ＣＲ＿２）单抗检测上皮细胞中该受体的表达已有报道，但对上皮细胞中ＥＢＶＲ／ＣＲ＿２的基因结构仍需研究。我们采用ＰＣＲ扩增和不对称ＰＣＲ直接测序法，首次检测了１０例ＮＰＣ及３例正常人胚鼻咽上皮（Ｈｕｍａｎｅｍｂｒｙｏｎｉｃｎａｓｏｐａｒｙｎｇｅａｌｅｐｉｔｈｅｌｉｕｍ，ＨＥＮＥ）组织样本中ＥＢＶＲ／ＣＲ＿２的ＥＢＶ结合区的编码序列。这一片段的ＤＮＡ序列测定结果显示，人ＮＰＣ细胞和正常ＨＥＮＥ细胞的ＥＢＶＲ／ＣＲ＿２的ＥＢＶ结合区的编码序列，与正常人Ｂ淋巴细胞的ＥＢＶＲ／ＣＲ＿２的相应序列完全相同，提示ＥＢＶ感染鼻咽上皮细胞可能与ＥＢＶＲ／ＣＲ＿２基因的ＥＢＶ结合区结构改变无直接关系。

定量检测EB病毒VCA-IgA抗体及EB病毒DNA对鼻咽癌筛查和诊断的价值

目的:探讨EB病毒VCA-IgA抗体和EB病毒DNA定量检测对鼻咽癌的筛查和诊断意义。方法:收集48例鼻咽癌患者、41例非鼻咽癌患者和6735例健康体检人群作为研究对象,采用化学发光法定量检测VCA-IgA抗体,实时荧光定量PCR法检测EBV-DNA浓度,以临床病理诊断为"金标准",分析指标的阳性率、灵敏度、特异性、阴性和阳性预测值。结果:鼻咽癌患者VCA-IgA抗体和EBV-DNA阳性检出率分别为91.6%(44/48)和52.1%(25/48),VCAIgA抗体的敏感度、准确度和阴性预测值高于EBV-DNA,但特异性和阳性预测值低于EBV-DNA;VCA-IgA抗体和EBV-DNA阴性预测值均大于99%,表明这2项指标均为阴性时,患鼻咽癌的风险较低;VCA-IgA抗体的ROC曲线下面积为95.19%,EBV-DNA为76.02%,两者均可用于诊断鼻咽癌。结论:定量检测VCA-IgA抗体水平及EB-DNA对鼻咽癌的筛查和诊断具有很大的临床价值。

呼吸道感染患儿EBV-DNA载量及与肝肾功能损伤的关系

目的探讨呼吸道感染患儿爱泼斯坦-巴尔病毒(EBV)-脱氧核糖核酸(DNA)载量表达及其与肝肾功能损伤的关系研究。方法选取2016年1月至2020年6月门诊及病房住院治疗经临床确诊的呼吸道感染儿童175例为研究对象,依据EBV-DNA载量水平分为阳性组(n=117)和阴性组(n=58),比较不同性别、年龄的呼吸道感染患儿EBV-DNA阳性率,根据EBV-DNA载量将阳性组患儿分为EBV-DNA高载量组(n=21)、中载量组(n=35)和低载量组(n=61),比较不同EBV-DNA载量组患儿肝肾功能异常比例及血清丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、胱抑素C(Cystatin C,CysC)、β2微球蛋白(β2-microglobulin,β2-MG)水平,Pearson相关性分析EBV-DNA载量与ALT、AST、CysC、β2-MG的关系。结果不同性别患儿间EBV-DNA阳性率差异无统计学意义(P>0.05),1~3岁、3~6岁年龄段儿童中EBV-DNA阳性率最高,不同年龄间患儿EBV-DNA阳性率差异有统计学意义(P<0.05);EBV-DNA低载量组、中载量组、高载量组的肝功能异常比例为19.67%、48.57%、66.67%,肾功能异常比例为13.11%、42.86%、52.38%,不同EBV-DNA载量患儿肝肾功能异常比例相比,差异有统计学意义(P<0.05);血清ALT、AST、CysC、β2-MG水平随EBV-DNA载量升高而升高(P<0.05),EBV-DNA载量与ALT、AST、CysC、β2-MG水平呈正相关性(P<0.05)。结论呼吸道感染患儿EBV-DNA载量升高会增加发生肝肾功能损伤的风险,且在1~6岁儿童EBV-DNA阳性率较高,检测EBV-DNA载量有助于呼吸道感染患儿肝肾功能的损伤的评估。

鼻咽癌血浆EBV-DNA浓度的微分动力学模型

目的通过建立微分方程模型,探讨鼻咽癌血浆Epstein-Barr病毒-DNA(EBV-DNA)含量在放疗中的动力学变化。方法选取2013年1月至2014年12月10例接受单纯放疗的鼻咽癌患者,采用荧光定量PCR检测其血浆EBV-DNA的动态表达水平。结果微分方程模型能很好地拟合血浆EBV-DNA的实际观测数据。模型参数与治疗中EBV-DNA的清除动力学特征有很好的相关性,且可能对患者的临床表型有一定的指示作用。结论微分方程模型参数可能提示肿瘤的生物学特性,但其意义价值尚需进一步验证。

鼻咽癌患者血浆游离EBV-DNA的研究进展

近年来,研究人员发现血浆游离EB病毒DNA对鼻咽癌的诊断、分期、疗效监测及判断预后方面都具有重要作用,并且优于目前较为普遍的抗体的检测,是新一代的有效检测指标。

吸烟对鼻咽癌患者治疗前血浆EBV-DNA表达和预后的影响

目的:研究吸烟与鼻咽癌(nasopharyngeal carcinoma,NPC)患者治疗前血浆EB病毒DNA(Epstein-Barr virus DNA,EBV-DNA)表达情况和预后的关系。方法 :选取首次确诊的477例男性NPC患者并留存治疗前静脉血,q RT-PCR检测NPC患者血浆EBV-DNA并计算吸烟指数,比较分析吸烟与NPC患者治疗前血浆EBV-DNA表达和预后的关系。结果:NPC患者的吸烟指数在治疗前T分期、N分期、M分期、临床分期等方面差异均无统计学意义(P>0.05)。不吸烟组与吸烟组EBVDNA阳性率和EBV-DNA拷贝数均无显著性差异(P=0.585,P=0.528);同时,不吸烟组与少量吸烟组和大量吸烟组EBVDNA阳性率和EBV-DNA拷贝数均无显著性差异(P=0.665,P=0.694);NPC患者的吸烟指数与治疗前血浆EBV-DNA拷贝数无显著相关性(P=0.536)。不吸烟组与吸烟组的肿瘤复发率和死亡率均无显著性差异(P=0.820,P=0.896),两组患者的无复发生存率和总生存率均无统计学差异(P=0.394,P=0.721);不吸烟组与少量吸烟组和大量吸烟组的肿瘤复发率和死亡率均无显著性差异(P=0.450,P=0.799),3组患者在无复发生存率和总生存率均无统计学差异(P=0.458,P=0.551)。Cox比例风险模型分析显示:T分期、N分期、M分期和治疗前EBV-DNA≥1 500 copies/m L是影响NPC患者无复发生存期的危险因素(P<0.05);年龄≥46岁、T分期、N分期、M分期和治疗前EBV-DNA≥1 500 copies/m L是影响NPC患者总生存期的危险因素(P<0.05);吸烟并不是影响NPC患者无复发生存期和总生存期的危险因素(P=0.946,P=0.673)。结论:吸烟对NPC患者治疗前血浆EBV-DNA表达和预后无显著影响。