血浆EBV DNA作为非流行地区鼻咽癌生物标志物的临床相关性：中国西南部的一项多中心研究。

Clinical relevance of plasma EBV DNA as a biomarker for nasopharyngeal carcinoma in non-endemic areas: A multicenter study in southwestern China.

作者信息

He Qiao, Zhou Yi, Zhou Jie, Zhao Dan, Li Luona, Li Xianbing, Huang Yecai, Wang Qiuju, Zou Haiming, Zhang Kaijiong, Li Yuping, Wang Zuo, Deng Yao, Meng Fanping, Ying Binwu, Yang Mu, Wang Dongsheng

机构信息

School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; Department of Clinical Laboratory, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Clin Chim Acta. 2023 Feb 15;541:117244. doi: 10.1016/j.cca.2023.117244. Epub 2023 Feb 4.

DOI:10.1016/j.cca.2023.117244

PMID:36746264

Abstract

BACKGROUND

Numerous clinical studies have validated plasma EBV DNA as a reliable biomarker for nasopharyngeal carcinoma (NPC) screening, tumor load monitoring, and prognosis prediction in endemic regions. However, the clinical relevance of plasma EBV DNA as a biomarker for NPC in non-endemic areas is still unclear.

METHOD

The pretreatment plasma EBV DNA of 1405 newly diagnosed NPC patients from three major regional hospitals in non-endemic areas were analyzed retrospectively. The medical records of 244 age- and gender-matched healthy individuals were reviewed. EBV DNA was detected using Polymerase Chain Reaction (PCR). Based on the baseline of 400 and 0 copies/mL, the distribution characteristics of the pretreatment EBV DNA load in different clinical stages and geographic regions were analyzed. The diagnostic value of pretreatment plasma EBV DNA for NPC with two baselines was evaluated using the ROC curve.

RESULTS

NPC patients had a significantly higher pretreatment EBV DNA level than healthy controls (P＜0.001). Pretreatment EBV DNA was closely associated with clinical and TNM stages in non-endemic areas, as it was in endemic areas. However, when 400 copies/mL set as the detection baseline, the sensitivity and specificity for NPC diagnosis were 40.8 % and 100 %, respectively (AUC = 0.704, cut off = 200.5 copies/mL). This sensitivity was lower than that reported in endemic regions (41.5 % - 97.1 %). Lower sensitivity may result in false negatives, missing diagnoses during NPC screening. Further investigation revealed that 39.7 % (558/1405) of NPC patients had detectable EBV DNA and S amplification curves. Optimizing the detection limit to 0 copies/mL, the sensitivity could be improved to 80.5 % (AUC = 0.901).

CONCLUSIONS

In non-endemic areas, the clinical significance of plasma EBV DNA as a biomarker for NPC was restricted due to the low detection limit of 400 copies/mL. More efficient nucleic acid extraction and detection methods are needed to optimize the detection limit and increase the clinical application of plasma EBV DNA for NPC.

摘要

背景

众多临床研究已证实，血浆EBV DNA作为一种可靠的生物标志物，可用于鼻咽癌（NPC）筛查、肿瘤负荷监测以及流行地区的预后预测。然而，在非流行地区，血浆EBV DNA作为鼻咽癌生物标志物的临床相关性仍不明确。

方法

回顾性分析来自非流行地区三家主要区域医院的1405例新诊断鼻咽癌患者的治疗前血浆EBV DNA。查阅244例年龄和性别匹配的健康个体的病历。采用聚合酶链反应（PCR）检测EBV DNA。以400拷贝/mL和0拷贝/mL为基线，分析不同临床分期和地理区域治疗前EBV DNA负荷的分布特征。采用ROC曲线评估两种基线水平下治疗前血浆EBV DNA对鼻咽癌的诊断价值。

结果

鼻咽癌患者治疗前EBV DNA水平显著高于健康对照（P＜0.001）。在非流行地区，治疗前EBV DNA与临床及TNM分期密切相关，与流行地区情况相同。然而，当以400拷贝/mL作为检测基线时，鼻咽癌诊断的敏感性和特异性分别为40.8%和100%（AUC = 0.704，临界值 = 200.5拷贝/mL）。该敏感性低于流行地区报道的敏感性（41.5% - 97.1%）。较低的敏感性可能导致假阴性，在鼻咽癌筛查过程中出现漏诊。进一步研究显示，39.7%（558/1405）的鼻咽癌患者可检测到EBV DNA且S扩增曲线呈阳性。将检测限优化至0拷贝/mL，敏感性可提高至80.5%（AUC = 0.901）。