HPV16-E6-DNA对宫颈癌预后预测价值分析  

Expression and prognostic significance of HPV16-E6-DNA in cervical carcinoma tissues after radical hysterectomy

作　　者：宋晓玲[1] 蔡红兵[2] 

机构地区：[1]湖北省妇幼保健院妇科,湖北武汉430070 [2]武汉大学中南医院妇瘤科.湖北省肿瘤医学临床研究中心.肿瘤生物学行为湖北省重点实验室,湖北武汉430071

出　　处：《中华肿瘤防治杂志》2015年第6期416-420,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81272866)

摘　　要：目的探讨宫颈癌组织中高危型人乳头瘤病毒(high risk human papillomavirus,HR HPV)16型的致癌基因E6(HPV16-E6-DNA)病毒载量情况及其对肿瘤预后的影响。方法收集2000-06-04-2006-12-08武汉大学中南医院妇瘤科134例宫颈癌患者,均首次诊断为宫颈癌,行宫颈癌根治性切除术,术后经病理确诊,且随访资料完整。提取石蜡组织DNA,将HPV16-E6亚克隆到pcDNA3.1-myc-HisA载体上,利用荧光定量PCR(RT-PCR)技术检测宫颈癌组织中HPV16-E6-DNA病毒载量,并采用Spearman相关分析、Kaplan-Meier和多因素Cox比例风险回归模型分析HPV16-E6-DNA病毒载量与各临床病理特征的相关性,及其对总生存率的影响。结果 HPV16-E6成功克隆到pcDNA3.1-myc-HisA载体上。相关性分析显示,HPV16-E6-DNA病毒载量在宫颈癌组织的表达水平与宫颈癌患者年龄(P<0.001)、FIGO分期(P<0.001)和淋巴结转移(P<0.001)相关。Kaplan-Meier生存分析显示,HPV16-E6-DNA病毒拷贝数>107组5年总生存率为39.4%,105~107组为44.0%,<105组为86.3%,差异有统计学意义,P<0.001。单因素分析显示,年龄(P<0.001)、HPV16-E6-DNA病毒载量(P<0.001)、病理分级(P=0.049)、FIGO分期(P<0.001)、深肌层浸润(P=0.001)、宫旁阳性(P=0.010)和淋巴结转移(P=0.012)是影响预后的主要因素。Cox回归分析显示,淋巴结转移(P=0.002)和HPV16-E6-DNA病毒载量(P=0.010)是预后的独立危险因素。结论宫颈癌组织中,HPV16-E6-DNA病毒载量明显增加,其表达是宫颈癌根治性切除术后的总体生存率的独立预后因素,可作为宫颈癌根治性切除术后的预后预测因子之一。OBJECTIVE To investigate the expression of high-risk types of human papillomavirus（HPV） oncogene （E6） in cervical cancer tissues and to analyze the association of HPV E6 expression with elinieopathologic characteristics and prognosis. METHODS One hundred and thirty-four patients from Zhongnan Hospital of Wuhan University who diag- nosed as cervical cancer after pathological analysis received radical hysterectomy from June 4,2000 to December 8,2006. DNA extracted from paraffin tissue, HPV16-E6 was cloned into the carrier of pcDNA3.1-myc-HisA. Their complete fol- low-up data were collected, and they were considered as study population. Rluorescenee quantitative PCR（RT-PCR） meth- od was used to detect the expression of HPV16-E6-DNA. The association of HPV16-E6-DNA expression with clin-ico- pathologic characteristics and overall survivals were analyzed using Spearman,Kaplan-Meier and Cox proportional hazard model. RESULTS HPV16-E6 was successfully cloned into the carrier of pcDNA3.1-myc-HisA. There was correlation be- tween HPV16-E6-DNA content with cervical cancer patients age（P〈 0. 001 ）, FIGO staging （P〈 0.001 ） and lymph node metastasis（P〈0. 001）. Kaplan-meier survival analysis showed that the overall 5-year survival rates of the viral copy num- ber range 〉 107 , 105 --107 ,〉107 of HPV16-E6-DNA were 39.4 %,44.0 % and 86.3 %, which were differently statistically significant （P〈0. 001）. Univariate analysis showed that the patient＇s age（P〈0. 001）, HPV16-E6-DNA viral load（P〈 0. 001） ,FIGO stage（P^0. 001） ,pathology classification（P〈0. 049） ,histological grade（P〈0. 001） ,deep myometrial in- vasion（P=0. 001）,parametrial positive（P=0. 010）,lymph node metastasis（P=0. 012） were the factors for poor overall survival time. Cox regression analysis showed that lymph node metastasis（P= 0. 002） and HPV16-E6 DNA viral load（P =0. 010） were independent prognostic factors. CONCLUSION HPV16-E6-DNA viral load increased significantly in cer- vica

关 键 词：宫颈肿瘤 人乳头瘤病毒 E6 预后 

分 类 号：R737.33[医药卫生—肿瘤]