鼻咽癌患者血浆EBV DNA、血清CYFRA21-1和VCA-IgA的检测及临床应用

目的：探讨血浆EB病毒DNA、血清细胞角蛋白19片段（CYFRA21-1）和EB病毒壳抗原IgA（VCA-IgA）三种肿瘤标记物对鼻咽癌诊断、疗效监测和预后判断的临床应用价值。方法：分别采用荧光定量PCR法、电化学发光法和免疫酶法检测62例鼻咽癌患者治疗前、后及62例健康对照者血浆EBV DNA、血清CY-FRA21-1和VCA-IgA含量,并进行对比分析。结果：治疗前血浆EBV DNA、血清CYFRA21-1和VCA-IgA的阳性率明显高于健康对照组（P〈0.01）;治疗后血浆EBV DNA、血清CYFRA21-1和VCA-IgA含量高者,在随访中发现肿瘤残存、复发或远处转移。结论：血浆EBV DNA、血清CYFRA21-1和VCA-IgA的检测对鼻咽癌早期诊断、高危人群筛查、以疗效监测和预后判断有重要临床应用价值,三种肿瘤标记物联合检测有互补作用。     

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. METHODS AND MATERIALS: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. RESULTS: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. CONCLUSION: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.     

EB病毒VCA-IgA抗体与鼻咽癌临床表现的分析

目的:了解EB病毒VCA-IgA与鼻咽癌临床表现的关系.方法:对梧州市肿瘤所门诊经病理确诊的鼻咽癌患者1868例,应用免疫酶法测定鼻咽癌病人血清中EB病毒VCA-IgA抗体.EB病毒VCA-IgA抗体测定结果与鼻咽癌患者的临床主要特征及分期进行分析.结果:EB病毒VCA-IgA抗体水平与鼻咽癌患者的性别无关;与患者各年龄组之间无显著差异;患者原发灶TO-T4其抗体水平有轻微上升,但无明显的波动;患者的临床分期Ⅰ～Ⅳ期根据病程的发展有逐渐升高的趋势;而早期(Ⅰ、Ⅱ)与晚期(Ⅲ、Ⅳ)期比较、颈部淋巴结N_0～N_3之间的比较有显著的差异.结论:结果分析提示EB病毒VCA-IgA抗体水平与鼻咽癌的发生及发展有密切关系.     

联合检测EB病毒不同抗体及EB病毒DNA在鼻咽癌血清学诊断中的价值

目的:评价EB病毒(EBV)抗衣壳抗原VCA-IgA抗体、抗早期抗原EA-IgA抗体、抗立即早期抗原Rta-IgG抗体和EBV-DNA检测在鼻咽癌诊断中的价值。方法:收集160例初治鼻咽癌,133例症状相似的非鼻咽癌患者和163名健康体检者的血清和血浆。采用酶联免疫法检测血清VCA-IgA、EA-IgA和Rta-IgG抗体的水平,用实时荧光定量PCR检测血浆EBV-DNA的相对含量。按鼻咽癌2008临床TNM分期法进行分期,计算不同分组、各临床分期以及鼻咽癌治疗前后的各抗体阳性率、抗体水平以及EB-DNA的检测结果并进行数据分析。结果:鼻咽癌组VCA-IgA、EA-IgA、Rta-IgG和EBV-DNA阳性率均高于鼻咽相关疾病组及健康对照组（均P<0.05）。血清VCA-IgA和EA-IgA结果相对A值（即rA或S/CO值）在Ⅰ、Ⅱ期低于Ⅲ、Ⅳ期,差异有统计学意义(P<0.05),但阳性率在各期间比较差异无统计学意义(P>0.05);Ⅰ、Ⅱ期患者Rta-IgG的rA值和阳性率明显低于Ⅲ、Ⅳ期患者(P<0.05);血浆中EBV-DNA阳性率及EBV-DNA中位数水平随着临床分期的升高而增高,Ⅰ、Ⅱ期与Ⅲ、Ⅳ期比较差异有统计学意义（P<0.05）。治疗有效（CR+ PR）患者的EBV-DNA含量明显低于治疗前水平（P<0.05）。结论:VCA-IgA、EA-IgA、Rta-IgG、EBV-DNA检测有助于鼻咽癌的辅助诊断、临床分期预测及疗效评估。     

Serologic diagnosis of nasopharyngeal carcinoma. A double-blind study of four EB virus antibodies with evaluation by sequential discrimination

It is generally known that a close relationship exists between Epstein-Barr Virus (EBV) and nasopharyngeal carcinoma (NPC). Recently, patients with early lesions of NPC have been detected in the general population by use of serologic mass survey. Using the double-blind method, we have studied the diagnostic value of the four EBV antibody titers, VCA-IgA, VCA-IgG, EA-IgA and EA-IgG, in four groups of subjects, each consisting of 50 persons: patients with nasopharyngeal carcinoma (NPC group), patients with cancers other than NPC in the head and neck regions (HNC group), patients with cancers outside of head and neck regions (OC group) and normal individuals (NS group). The results of these four antibodies were evaluated both singularly and together by multivariate sequential discrimination. Taking 1:10 as the criterion of being positive, in the NPC group, the positive rate of VCA-IgA is 88%, the VCA-IgG rate is 100%, the EA-IgA rate is 48% and the EA-IgG rate is 74%. In the non-NPC group, the positive rates of VCA-IgA are as high as 86%-92%, but those of the other antibodies are as low as 0-42%. The positive rates and the geometric mean titers of these four antibodies were all elevated as compared with those in the three non-NPC groups. These differences are statistically significant. VCA-IgG is unimportant in the diagnosis of NPC because of its low specificity. By treating the antibody titers of VCA-IgA, VCA-IgG, EA-IgA and EA-IgG with sequential discrimination, the correlation rate between the serology and pathology of NPC is 88% and the false positive rate is 7.3%.     

鼻咽癌咽后淋巴结转移与 EBV-DNA 血清学标记物关系探讨

目的:探讨鼻咽癌患者咽后淋巴结转移与EB病毒血清学标志物的关系.方法:收集首诊鼻咽癌患者721例,按“中国鼻咽癌2008 TNM分期”标准对咽后淋巴结进行判断并分为咽后淋巴结转移阳性组与阴性组,分别记录每个病例EB病毒血清学标记物:EB-DNA拷贝数、EB-VCA抗体滴度、EA-IgA抗体滴度,统计咽后淋巴结有转移组与无转移组与EB病毒血清学标记物:EB-DNA拷贝数、VCA-IgA抗体滴度、EA-IgA抗体滴度的关系.结果:鼻咽癌患者咽后淋巴结阳性者较阴性组有较高的EB-DNA拷贝数,差异有显著统计学意义(P＜0.01);不同VCA-IgA抗体滴度下咽后淋巴结的阳性率不同,差异有统计学意义(P＜0.05),VCA-IgA抗体滴度越高咽后淋巴结阳性率越高;不同EA-IgA抗体滴度下咽后淋巴结的转移率不同,差异有显著统计学意义(P＜0.05),EA-IgA抗体滴度越高咽后淋巴结阳性率越高.结论:鼻咽癌患者咽后淋巴结转移与EB病毒血清学标记物:EB-DNA拷贝数、VCA-IgA抗体滴度、EA-IgA滴度呈正相关.     

EA-D p45-IgG as a Potential Biomarker for Nasopharyngeal Carcinoma Diagnosis

Aim: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit. Methods:Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles weretested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores ofintensity visually assigned to the protein bands. The markers which showed statistical differences between theNPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparisonwith established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. Results:Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPCand non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects,the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negativepredictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were75.0% and 90.6 %, respectively. Conclusions: EA-D p45-IgG might be a potential biomarker for NPC diagnosis,especially among VCA-IgA positive subjects.     

Gene engineering EB virus membrane antigen in detection of MA-IgA antibody

With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluorescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.     

Disparity of sensitivities in detection of radiation-na?ve and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein-Barr virus DNA1,2.

PURPOSE: The purpose of this research was to compare the sensitivities of plasma EBV DNA in detection of postirradiation locally recurrent nasopharyngeal carcinoma (NPC), postirradiation distant metastatic NPC, and radiation-na?ve NPC. EXPERIMENTAL DESIGN: Twenty-four patients with postirradiation local recurrence of NPC were assessed for plasma EBV DNA levels by a real-time quantitative PCR system. The results were compared with those of a cohort of 140 patients with newly diagnosed NPC and with those of 25 patients with distant metastatic relapse. EBV-encoded RNA positivity was also assessed in locally recurrent tumors and newly diagnosed tumors with undetectable plasma EBV DNA levels. RESULTS: Postirradiation locally recurrent tumors were associated with a significantly lower rate of detectable plasma EBV DNA compared with radiation-na?ve tumors of comparable stage [stage I-II tumors: 5 of 12 (42%) versus 47 of 51 (92%), P = 0.0002; stage III-IV tumors: 10 of 12 (83%) versus 88 of 89 (99%), P = 0.01; Fisher's exact test], and compared with distant metastatic recurrences [15 of 24 (63%) versus 24 of 25 (96%), P < 0.02; Fisher's exact test]. The median EBV DNA level in patients with detectable EBV DNA was also significantly lower in locally recurrent tumors than in radiation-na?ve tumors. All of the tissue samples of tumors associated with undetectable EBV DNA levels, where available, were EBV-encoded RNA positive. CONCLUSIONS: The sensitivity of EBV DNA in the detection of tumors regrowing from an irradiated site is much lower than that from a radiation-na?ve site. Although plasma EBV DNA is very effective in detecting distant metastatic relapse of NPC, it cannot be relied on as the sole surveillance tool for detection of local relapse.     

基因工程膜抗原检测EB病毒MA—IgA抗体研究及与VCA—IgA...

With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluorescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pre-treatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.     

鼻咽癌患者外周血循环肿瘤细胞的检测及其与预后的相关性

目的:利用抗体标记和流式细胞仪联合方法检测鼻咽癌外周血中的循环肿瘤细胞(circulating tumor cells,CTCs)数量,分析评价CTCs与患者临床特征和预后之间的相关性.方法:针对福建省肿瘤医院2012年7月至2014年5月收治的67例鼻咽癌首诊患者以及10例健康志愿者,抽取外周血10ml,提取其中的单个核细胞.依次应用抗Epcam、抗CD45以及抗CK单克隆抗体对上述提取的单个核细胞进行抗体标记,将Epcam阳性、CD45阴性以及CK阳性的细胞作为鼻咽癌患者的CTCs,应用流式细胞仪检测其在外周血中的存在情况,分析其与患者临床特征及预后之间的关系.结果:鼻咽癌组外周血中的CTCs明显高于健康志愿者组,差异具有统计学意义(P<0.05).单因素分析结果表明,鼻咽癌患者外周血CTCs水平与进展情况(P=0.04)、N分期(P=0.001)以及临床分期(P=0.035)均显著相关.Logistic多因素回归分析结果则显示,仅患者的N分期与CTCs水平具有相关性(P=0.003),CTCs阳性患者的N分期更晚.Kaplan-Meier生存分析显示,CTCs阳性患者的无进展生存期(progression free survival,PFS)要显著短于CTCs阴性患者(P=0.029).结论:鼻咽癌患者外周血中CTCs阳性与患者N分期相关,且提示预后不良,可能成为鼻咽癌患者预后评估的一个辅助指标.     

Relationship of circulating tumor cells and Epstein–Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients

We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.     

血清DKK1和EB病毒VCA-IgA联合检测对鼻咽癌的诊断价值

目的：探讨血清Dickkopf-1（DKK1）和EB病毒壳抗体（VCA-IgA）联合检测在鼻咽癌中的诊断价值。方法应用酶联免疫吸附试验检测80例鼻咽癌患者和65例正常对照者血清DKK1和VCA-IgA的水平,采用受试者工作特征（ROC）曲线评价诊断效能。结果鼻咽癌患者血清DKK1的表达水平明显高于正常对照组[580．773（429．146）pg／ml ∶316．174（252．965）pg／ml],差异有统计学意义（Z＝4．846,P＜0．0001）。ROC曲线显示血清DKK1对鼻咽癌的最佳诊断临界值为611．981 pg／ml,其诊断曲线下面积（AUC）为0．734（95％CI为0．654～0．815）,敏感性为50．0％,特异性为96．9％。VCA-IgA对鼻咽癌的诊断AUC为0．714（95％CI为0．631～0．798）,敏感性为47．5％,特异性为95．4％。DKK1和VCA-IgA联合检测的诊断AUC为0．849（95％CI为0．783～0．914）,敏感性为76．3％,特异性为95．4％。早期鼻咽癌患者DKK1和VCA-IgA联合检测效果优于正常对照组,差异有统计学意义（χ2＝23．784,P＜0．001）。结论血清DKK1对鼻咽癌具有潜在的诊断价值,联合检测VCA-IgA有助于鼻咽癌的早期诊断。     

Pretherapy quantitative measurement of circulating Epstein-Barr virus DNA is predictive of posttherapy distant failure in patients with early-stage nasopharyngeal carcinoma of undifferentiated type

BACKGROUND: Patients with International Union Against Cancer (UICC) Stage I-II nasopharyngeal carcinoma (NPC) appear to have a relatively favorable prognosis and generally are excluded from trials of combined modality treatment. More recently, plasma/serum cell-free Epstein-Barr virus (EBV) DNA has been shown to be measurable in the majority of NPC patients at the time of diagnosis, and appears to have prognostic significance. However, within Stage I-II disease, in which failure events are infrequent, the prognostic impact of the pretreatment EBV DNA level has not been addressed to our knowledge. This issue has management implications because different therapeutic strategies currently are employed for patients with good-risk and those with poor-risk NPC. METHODS: A cohort of 90 patients with UICC Stage I-II NPC (World Health Organization Grade 2/3 histology) had their pretherapy plasma/serum EBV DNA levels determined by a quantitative polymerase chain reaction assay and correlated with the probability of posttherapy failure. All patients received radiation therapy only, except for three patients who also received concurrent chemotherapy. Kaplan-Meier plots of the probability of locoregional failure, distant failure, and cancer-specific survival were compared with reference to clinical stage and EBV DNA levels. RESULTS: With a median follow-up time of 45 months, 12 patients and 7 patients, respectively, had developed locoregional and distant failures, including 2 patients with both local and distant failures. Patients with distant failure had significantly higher pretherapy EBV DNA levels than those without failure (a median of 13,219 copies/mL [interquatile-range, 274,635 copies/mL] vs. a median of 423 copies/mL [interquatile-range, 2753 copies/mL]). The probability of distant failure was significantly higher in patients with high (>4000 copies/mL plasma) compared with low EBV DNA levels (P=0.0001, log-rank test) and for Stage IIB disease compared with Stage I and Stage IIA disease combined (P=0.0149, log-rank test), but was not significantly different between patients with Stage II and those with Stage I disease. The risks of locoregional failure were not significantly different between patients with high and those with low EBV DNA levels, and also was not significantly different between clinical substages. Approximately 35% of patients with Stage IIB disease were in the at-risk group for distant failure, as identified by high EBV DNA levels. CONCLUSIONS: Within a group of patients with UICC Stage I-II NPC, the pretherapy plasma EBV DNA level was found to identify a poor-risk group with a probability of distant failure similar to that of patients with advanced stage disease. This group of patients may warrant management considerations currently applicable only to cases of Stage III-IV disease. The prognostic significance of designating Stage IIB disease as per the 1997 UICC staging was confirmed, although the pretherapy EBV DNA level appears to be a more powerful prognostic discriminator in patients with early-stage NPC.     

鼻咽癌病人外周血和骨髓中的EB病毒与预后的临床相关性

目的通过检测NPC病人治疗前外周血和骨髓中EBV,研究EBV与NPC放疗后失败及远期生存的临床相关性.方法1998年2月至同年8月,选择诊断明确的27例晚期NPC病人,其中24例为初治、3例为局部复发,疗前用常规PCR分别检测外周静脉血和骨髓中EB病毒.同时检测13例非NPC肿瘤病人静脉血中的EBV,作为对比.结果13例非NPC病人静脉血中EB病毒均为阴性.27例NPC中,15例EBV阳性(外周血和骨髓中EBV均阳性者13例),阳性病例中有10例治疗失败,失败率66.7%,其中6例为远处转移,远处转移率40.0%.12例阴性病人,3例疗后失败,失败率25.0%:其中仅1例为远处转移,远处转移率8.3%.两组间失败率差异明显.结论部分NPC病人外周血和骨髓中疗前即存在着EB病毒.EBV阳性组放疗后失败的发生率明显高于EBV阴性组,而且外周血与骨髓EBV有很好的相关性,提示外周血EBV的检测在临床上具有判定预后的应用价值.     

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 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% 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 ana-lyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood sam-ples 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 were 82.2% 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). Multi-variate 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.     

EB病毒诱导下鼻咽癌患者外周血淋巴细胞的转化和退变

已感染EB病毒(EBV)者,如再次用EBV刺激,可出现外周血淋巴细胞转化细胞团的退变。本文观察阳性正常人20例、VCA—IgA阳性鼻咽癌(NPC)病人11例外周血淋巴细胞的这种转化和退变,全部阳性组受试者都出现B淋巴细胞转化,且转化细胞团的退变十分显著,仅少数转化细胞可以传代;而阳性NPC组转化时间提前,转化更完全,但退变出现的时间推迟,程度也较轻。作者认为,转化细胞团的退变,可间接反映特异性杀伤性T淋巴细胞的功能,因此,鼻咽癌病人T细胞免疫功能是降低的。     

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.     

鼻咽癌围放疗期EB病毒IgA抗体水平的变化

目的:探讨鼻咽癌围放疗期EB病毒免疫球蛋白A（IgA）抗体水平变化的价值。方法:选自我院于2014年4月至2017年3月期间收治的鼻咽癌患者61例;另选自我院于2014年4月至2017年3月行EBV血清学检测的50例健康者作为对照组。空腹采集外周静脉血,分离血清,采用ELISA法测定衣壳抗原IgA（VCA-IgA）和早期抗原IgA（EA-IgA）水平。比较两组VCA-IgA和EA-IgA抗体水平,鼻咽癌患者放疗前后VCA-IgA和EA-IgA抗体水平和阳性率,及VCA-IgA和EA-IgA联合诊断灵敏度和特异度。结果:观察组VCA-IgA和EA-IgA抗体水平高于对照组,且有统计学差异（P<0.05）;鼻咽癌患者放疗后VCA-IgA和EA-IgA抗体水平低于放疗前,且有统计学差异（P<0.05）;鼻咽癌患者放疗后VCA-IgA和EA-IgA阳性率低于放疗前,且有统计学差异（P<0.05）;鼻咽癌患者VCA-IgA和EA-IgA联合诊断灵敏度和特异度高于VCA-IgA和EA-IgA单项诊断。结论:VCA-IgA和EA-IgA用于鼻咽癌患者治疗效果评估具有重要价值,且联合诊断灵敏度和特异度较高,具有重要研究意义。     

血浆EB病毒DNA浓度预测鼻咽癌远处转移的研究

背景与目的：鼻咽癌治疗失败的主要原因之一是远处转移,近年多项放化疗综合治疗的临床研究未显示出明显的远处转移率的降低和远期生存的获益,综合治疗适宜个体及最佳模式尚未确立。血浆EB病毒DNA（EBV DNA）浓度是一项能反映鼻咽癌分期、治疗反应、预后的灵敏、特异的分子生物学指标。我们设计此前瞻性研究。探讨通过鼻咽癌患者血浆EBV DNA浓度预测远处转移的发生．为个体化的综合治疗模式的选择提供分子学指标。方法：69例初治鼻咽癌患者分别在治疗前和治疗结束时采用荧光定量PCR方法检测血浆EBV DNA浓度。所有患者按计划随访。进行远期疗效及生存的评价。Kaplan-Meier法计算无转移生存率及总生存率,多因素分析用Cox回归模型。结果：远处转移患者治疗前血浆EBV DNA中位浓度（27 000copies／m1）及治疗后EBVDNA检出率（55．56％）均高于持续缓解者（4 000 copies／ml,5．56％）及局部复发者（3 850 copies／ml,0％）（P值分别为0．039,0．001）。以治疗前20 000 copies／ml、治疗后0 copies／ml为界值点．EBV DNA低浓度患者的无复发生存率、无转移生存率及总生存率均高于高浓度患者,差异有显著性。Cox回归分析显示治疗前EBV DNA浓度（P=0．050,RR=3．95）、治疗后EBVDNA浓度（P=0．001,RR=11．74）均是影响无转移生存的危险因素。进一步将患者治疗前后EBVDNA浓度变化综合进行生存分析,结果表明治疗后EBV DNA浓度能否降到0是影响无转移生存最重要的预后因素（P=0．000）。结论：鼻咽癌患者治疗前、后血浆EBV DNA浓度,尤其是治疗后能否降到0．能预测远处转移的发生,有望为放化综合治疗筛选高危患者,指导放化结合模式的选择。