喉鳞状细胞癌组织CLDN11基因启动子甲基化及临床意义研究  

CLDN11 promoter methylation in laryngeal squamous cell carcinoma and its clinical significance

作　　者：曹炳 沈志森[2] 林乐希 郝文娟[1] 周重昌 Cao Bing;LIN Lexi;SHEN Zhisen(School of Medicine,Ningbo University,Ningbo 315000,China)

机构地区：[1]宁波大学医学院,315000 [2]宁波大学附属李惠利医院耳鼻咽喉头颈外科

出　　处：《浙江医学》2018年第5期425-428,共4页Zhejiang Medical Journal

基　　金：浙江省自然科学基金(LY14H160003);浙江省医药卫生省部培育计划(2014PYA017);浙江省医药卫生科技计划项目(2012ZDA042);宁波市科技创新团队(2012B82019;2015B11050);宁波市重大择优委托项目(2012C5015);宁波市自然科学基金(2012A610208;2017A610236)

摘　　要：目的探讨喉鳞状细胞癌(LSCC)组织中CLDN11基因启动子的甲基化水平及其临床意义。方法采用实时荧光定量甲基化特异性聚合酶链反应(q MSP)分别检测91例LSCC患者的LSCC组织及其配对的癌旁正常组织CLDN11基因启动子甲基化水平,分析其与临床病理特征及预后的关系,绘制ROC曲线评估其诊断价值。结果 LSCC组织CLDN11基因启动子甲基化水平明显高于癌旁正常组织(P<0.01)。Ⅲ、Ⅳ期、T_(3~4)期、有淋巴结转移的LSCC组织CLDN11基因启动子甲基化水平分别高于Ⅰ、Ⅱ期、T_(1~2)期、无淋巴结转移的LSCC组织(均P<0.01)。ROC曲线分析AUC为0.884(95%CI:0.835~0.932,P<0.01),甲基化水平为0.571时,诊断LSCC的灵敏度、特异度分别为0.923、0.736。与低甲基化组(甲基化水平<0.571)患者相比,高甲基化组(甲基化水平≥0.571)患者总生存率较低(P<0.01)。结论 CLDN11基因启动子高甲基化或可作为LSCC诊断和预测预后的生物标志物。Objective To investigate the methylation level of CLDN11promoter in laryngeal squamous cell carcinoma(LSCC)and its clinical significance.Methods The methylation level of CLDN11in91LSCC tissues and their paired normal tissues was measured by quantitative methylation-specific polymerase chain reaction(qMSP),and the relationship of CLDN11methylation with clinicopathologic features and prognosis of LSCC patients was evaluated.The diagnostic value of CLDN11methylation in LSCC was analyzed with receiver operating characteristic(ROC)curve.Results The methylation level of CLDN11in LSCC was significantly higher than that in adjacent tissues(P<0.01).CLDN11methylation was increased in patients with clinical stageⅢ/Ⅳ,T3~4classification and lymph node metastasis compared with that in patients withⅠ/Ⅱclinical stage,T1~2classification and without lymph node metastasis(all P<0.01).The area under the ROC curve(AUC)of CLDN11was0.884(95%CI=0.835-0.932,P<0.01);when the methylation level0.571was taken as cutoff value,the sensitivity and specificity of CLDN11methylation for diagnosis of LSCC were0.923and0.736,respectively.Patients with hypermethylation of CLDN11promoter(PMR≥0.571)had a lower overall survival than patients with hypomethylation(PMR<0.571).Conclusion CLDN11promoter hypermethylation may serve as a biomarker for the diagnosis and prognosis of LSCC.

关 键 词：喉鳞状细胞癌 CLDN11基因 DNA甲基化 生物标志物 

分 类 号：R739.65[医药卫生—肿瘤]