中国南方地区EBV高危亚型与鼻咽癌之间的关系  

Association between EBV-related high-risk subtypes and nasopharyngeal carcinoma in southern China

作　　者：李雪琪 席俊彦 谢尚杭 林冬丰 周杭宁 马征 彭一楠 曹素梅 LI Xueqi;XI Junyan;XIE Shanghang;LIN Dongfeng;HOU Hangning;MA Zheng;PENG Yinan;CAO Sumei(School of Public Health,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Department of Cancer Prevention,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510080,China;State Key Laboratory of Oncology in South China,Guangzhou,Guangdong 510080,China;Sun Yat-sen Global Health Institute,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Center for Health Information Research,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangzhou,Guangdong 510080,China;Guangdong Provincial Clinical Research Center for Cancer,Guangzhou,Guangdong 510080,China;School of Public Health,Guangdong Medical University,Dongguan,Guangdong 523808,China)

机构地区：[1]中山大学公共卫生学院,广东广州510080 [2]中山大学肿瘤防治中心肿瘤预防研究部,广东广州510080 [3]华南恶性肿瘤防治全国重点实验室,广东广州510080 [4]中山大学全球卫生研究中心,广东广州510080 [5]中山大学卫生信息研究中心,广东广州510080 [6]广东省鼻咽癌诊治研究重点实验室,广东广州510080 [7]广东省恶性肿瘤临床医学研究中心,广东广州510080 [8]广东医科大学公共卫生学院,广东东莞523808

出　　处：《热带医学杂志》2024年第6期769-775,787,共8页Journal of Tropical Medicine

基　　金：国家自然科学基金面上项目(82073625,82373655);广东省自然科学基金面上项目(2023A1515010221)。

摘　　要：目的 基于在中国南方开展的一项病例对照研究,分析不同样本来源的Epstein-Barr病毒(EBV)高危亚型与鼻咽癌发生风险的关系,并评估其在鼻咽癌诊断中的价值。方法 于2020-2021年在广东省招募150例新诊断鼻咽癌患者(鼻咽癌组)和150名非鼻咽癌健康人群(对照组),病例分别来自中山大学肿瘤防治中心鼻咽科及广东省四会癌症中心鼻咽癌高发区筛查队列。采用酶联免疫吸附试验检测EBV衣壳抗原IgA抗体(VCA-IgA)和EBV潜伏感染时表达的核抗原1 IgA抗体(EBNA1-IgA),并计算EBV抗体评分。同时采用多重PCR法,对鼻咽刷子和唾液中EBV高危亚型(BALF2_162476T>C、BALF2_163364C>T、BALF2_162215C>A、RPMS1_155391G>A、LMP1_WT>del)检测,分析其与鼻咽癌发生风险的关系,比较EBV抗体评分及不同标本来源BALF2对鼻咽癌的诊断效果,进一步将二者联合并评估其对鼻咽癌鉴别诊断的效能。结果 鼻咽癌组晚期(Ⅲ、Ⅳ期)占90.67%(136/150),早期(Ⅰ、Ⅱ期)占9.33%(14/150)。鼻咽癌组中EBV抗体评分为高危占80%,高于对照组的2%,差异有统计学意义(χ^(2)=227.024,P<0.001)。鼻咽癌组鼻咽刷子中5种高危亚型(BALF2_162476T>C、BALF2_163364C>T、BALF2_162215C>A、RPMS1_155391G>A、LMP1_WT>del)阳性率均高于对照组,差异均有统计学意义(χ^(2)=18.766、21.054、59.883、26.124、20.402,P均<0.001);其中鼻咽癌组、对照组中LMP1_WT>del阳性率最高分别为93.84%、71.08%;所有亚型检出率在早晚期患者之间差异均无统计学意义(P均>0.05)。鼻咽癌组唾液来源BALF2_162476T>C、BALF2_163364C>T、BALF2_162215C>A、RPMS1_155391G>A阳性率均高于对照组,差异均有统计学意义(χ^(2)=8.063、8.633、8.033、14.909,P均<0.05);其中晚期患者BALF2_162215C>A检出率高于早期(85.59%vs. 55.56%),差异有统计学意义(P=0.041);其余高危亚型检出率在早晚期患者之间差异均无统计学意义(P均>0.05)。鼻咽刷子来源BALF2_162215C>A与鼻咽癌风险关系最�Objective Based on a case-control study conducted in southern China, this study analyzed the association between Epstein-Barr virus(EBV)-related high-risk subtypes from different resources and the risk of nasopharyngeal carcinoma and then evaluated their value in the diagnosis of nasopharyngeal carcinoma. Methods A total of 150 newly diagnosed patients with nasopharyngeal carcinoma(nasopharyngeal cancer group) and 150 healthy people without nasopharyngeal carcinoma(control group) in Guangdong province were recruited for the study;nasopharyngeal carcinoma cases were recruited from Sun Yat-sen Cancer Center and Sihui Cancer Center, in 2020-2021. Enzyme-linked immunosorbent assay(ELISA)was used to detect viral capsule antigen IgA antibodies(VCA-IgA)and EBV nuclear antigen 1IgA antibodies(EBNA1-IgA),and the EBV antibody score was calculated. At the same time,a multiplex PCR system was developed to detect EBV high-risk subtypes(BALF2_162476T>C, BALF2_163364C>T, BALF2_162215C>A,RPMS1_155391G>A and LMP1_WT>del) in nasopharyngeal swabs and saliva, and to analyze the relationship between subtypes and the risk of nasopharyngeal carcinoma. The diagnostic efficacy of EBV antibody score and EBV BALF2 in different samples were compared, and were comprehensively evaluated their efficacy in the differential diagnosis of nasopharyngeal carcinoma.Results In the nasopharyngeal cancer group, late stage(stage III and IV) accounted for 90.67%(136/150), and early stage(stage I and II) accounted for 9.33%(14/150). In the nasopharyngeal cancer group, 80% had high-risk EBV antibody scores, which was higher than 2% in the control group, and the difference was statistically significant (χ^(2)=227.024,P<0.001). The positive rates of five high-risk subtypes(BALF2_162476T>C, BALF2_163364C>T, BALF2_162215C>A, RPMS1_155391G>A, LMP1_WT>del) in nasopharyngeal swabs in the nasopharyngeal cancer group were all higher than those in the control group, and the differences were statistically significant (χ^(2)=18.766,21.054,59.883,26.124,20.402;all P<

关 键 词：鼻咽癌 EBV抗体评分 EBV BALF2 诊断试验 病例对照设计 

分 类 号：R739.63[医药卫生—肿瘤]