HPV-DNA整合状态与宫颈癌发生发展及抑癌基因p53、pRb表达的相关性  

Correlation between HPV-DNA integration and cervical cancer development as well as the expression of cancer suppressor gene p53 and pRb

作　　者：温川松 仝进毅[1] 

机构地区：[1]浙江省杭州市第一人民医院,南京医科大学附属杭州医院妇科,浙江杭州310000

出　　处：《中国临床药理学与治疗学》2017年第2期155-159,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省自然科学基金项目(LY12H16018)

摘　　要：目的:分析人乳头瘤病毒(HPV)-DNA整合状态与宫颈癌发生发展及抑癌基因p53、pRb表达的关系,为其临床诊治提供新思路。方法:取本院收治、手术治疗的宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌患者131例,根据病变程度分为CINⅠ、CINⅡ、CINⅢ和宫颈癌4组,取同期收治的良性瘤患者33例为对照,术中留取病理组织,采用全基因组测序和高通量病毒整合实验观察HPV-DNA整合状态。进一步根据整合状态分为多重整合、单重整合和无整合3组,采用免疫组织化学实验观察抑癌基因p53、pRb的表达水平。结果:各组HPV-DNA整合率不同,自健康组织、CINⅠ、CINⅡ、CINⅢ、宫颈癌的顺序依次升高,且宫颈癌以多重整合为主,健康组织和CIN以单一整合为主,组间差异有统计学意义(P<0.05)。本次考察发现HPV16、HPV58、HPV18、HPV35、HPV31、HPV33、HPV52、HPV51 8种高危HPV整合类型,在各组中的分布趋势大体一致。不同整合状态的p53、pRb阳性率和表达水平明显不同,无整合组高于单重整合组,单重整合组高于多重整合组,其组间差异均有统计学意义(P<0.05)。结论:HPV-DNA整合能抑制p53与pRb的局部表达,促进宫颈癌发展,对宫颈癌鉴别和预后评估有一定的指导作用。AIM：To analyze the correlation between HPV-DNA integration and cervical cancer development as well as the expression of cancer suppressor gene p53 and pRb,so as to provide new idea for its clinical diagnosis and treatment.METHODS：131 patients with cervical intraepithelial neoplasias （CIN） and cervical cancer which treated with surgery were selected and divided into 4 groups according to disease degree：CIN Ⅰ,CIN Ⅱ,CIN Ⅲ and cervical cancer;at the same time,33 patients with benign tumor were selected as controls.The pathological tissues were extracted and detected HPV-DNA integration using whole genome sequencing and high-throughput virus integrated experiment.According to HPV-DNA integration results,all the patients were divided into 3 groups：multi-integration,single-integration and non-integration,and the p53 and pRb expression levels between groups were compared.RESULTS：The HPV-DNA integration rate increased according to the healthy tissue,CIN Ⅰ,CIN Ⅱ,CIN Ⅲ,cervical cancer in the order,and there was mainly multi-integration in the cervical cancer,and mainly single-integration in CIN and the controls,the difference between groups had statistical significance （P 〈 0.05）.8 types of high-risk HPV-DNA integration,including HPV16,HPV58,HPV18,HPV35,HPV31,HPV33,HPV52 and HPV51 were found,with similar distribution trend in different disease degree.The p53 and pRb positive rate and expression level were different in different integration state,and non-integration group was higher than single-integration group,single-integration group was higher than multi-integration group,the difference between groups had statistical significance （P 〈 0.05）.CONCLUSION：HPV-DNA integration can restrain the expression of p53 and pRb and promote the development of cervical cancer,which may have a certain guiding role for the identification and prognosis evaluation of cervical cancer.

关 键 词：人乳头瘤病毒 DNA整合 宫颈癌 抑癌基因 

分 类 号：R968[医药卫生—药理学] R737.3[医药卫生—药学]