一项评估血浆 Epstein-Barr 病毒标志物用于鼻咽癌患者早期诊断的随机对照试验。

A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma.

机构信息

Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.

出版信息

Adv Ther. 2020 Oct;37(10):4280-4290. doi: 10.1007/s12325-020-01461-4. Epub 2020 Aug 11.

DOI:10.1007/s12325-020-01461-4

PMID:32780356

Abstract

INTRODUCTION

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a major problem in Southern China. Epstein-Barr virus (EBV) biomarkers have been widely used in NPC screening. This study aims to evaluate the early diagnostic performances of individual EBV biomarkers in NPC.

METHODS

The levels of EBV biomarkers-IgA antibodies against EBV nuclear antigen 1 (EBNA1-IgA), EBV capsid antigen (VCA-IgA), EBV early antigen (EA-IgA), EBV BZLF1 transcription activator protein (Zta-IgA) and IgG antibodies against EBV BRLF1 transcription activator protein (Rta-IgG)-from 106 NPC patients (stage I and II) and 150 normal subjects were measured. VCA-IgA and EA-IgA were detected by immunofluorescence assay (IFA), EBNA1-IgA, Rta-IgG and Zta-IgA were measure by enzyme-linked immunosorbent assay (ELISA), and EBV DNA was detected by qPCR. Statistical analyses of a single index were conducted to evaluate the significance of NPC early diagnosis and TNM classification.

RESULTS

The level of EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA, Rta-IgG and Zta-IgA in early-stage NPC was significantly higher than in healthy controls (all P < 0.001). EBNA1-IgA yielded the biggest area under the curve (AUC) of 0.962 in distinguishing early-stage NPC patients from the normal subjects, with a sensitivity of 91.5% and a specificity of 98.7%. However, EBV biomarker levels were not associated with tumor size (all P > 0.050), whereas four biomarker levels (EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA) were related to lymph node metastasis (N0 and N1-2), among which EBNA1-IgA and EBV DNA showed good performance. Finally, high correlation was found between VCA-IgA and EA-IgA (r > 0.800).

CONCLUSION

A single EBNA1-IgA exhibits excellent discrimination performance in early diagnosis of NPC and could become a promising marker for NPC screening.

摘要

简介

在华南地区，早期诊断鼻咽癌（NPC）仍然是一个主要问题。EB 病毒（EBV）标志物已广泛应用于 NPC 的筛查。本研究旨在评估单个 EBV 标志物在 NPC 中的早期诊断性能。

方法

检测了 106 例 NPC 患者（I 期和 II 期）和 150 例正常对照者的 EBV 标志物-IgA 抗体针对 EBV 核抗原 1（EBNA1-IgA）、EBV 衣壳抗原（VCA-IgA）、EBV 早期抗原（EA-IgA）、EBV BZLF1 转录激活蛋白（Zta-IgA）和 IgG 抗体针对 EBV BRLF1 转录激活蛋白（Rta-IgG）的水平。VCA-IgA 和 EA-IgA 通过免疫荧光法（IFA）检测，EBNA1-IgA、Rta-IgG 和 Zta-IgA 通过酶联免疫吸附法（ELISA）检测，EBV DNA 通过 qPCR 检测。对单项指标的统计学分析用于评估 NPC 早期诊断和 TNM 分期的意义。

结果

早期 NPC 患者的 EBNA1-IgA、EBV DNA、VCA-IgA、EA-IgA、Rta-IgG 和 Zta-IgA 水平显著高于健康对照组（均 P<0.001）。EBNA1-IgA 在区分早期 NPC 患者和正常对照者方面产生了最大的曲线下面积（AUC）0.962，灵敏度为 91.5%，特异性为 98.7%。然而，EBV 标志物水平与肿瘤大小无关（均 P>0.050），而四种标志物水平（EBNA1-IgA、EBV DNA、VCA-IgA、EA-IgA）与淋巴结转移（N0 和 N1-2）有关，其中 EBNA1-IgA 和 EBV DNA 表现出良好的性能。最后，VCA-IgA 与 EA-IgA 之间存在高度相关性（r>0.800）。