摘要
目的探讨人乳头瘤病毒(HPV)16早期基因E2和E6与核不均一核糖核蛋白(hnRNP)E2在宫颈癌变中的作用及其交互效应。方法研究对象来源于课题组在山西省介休市建立的"自然人群宫颈病变队列",以2014年6—9月经病理学确诊的正常宫颈(NC)女性、低度宫颈上皮内瘤变(CINⅠ)、高度宫颈上皮内瘤变(CINⅡ/Ⅲ)以及同期在山西医科大学第二医院确诊的宫颈鳞状细胞癌(SCC)病例为研究对象。共纳入257名研究对象,NC、CINⅠ、CINⅡ/Ⅲ、SCC组分别为67名(26.07%)、69例(26.85%)、68例(26.46%)、53例(20.62%)。采用问卷调查收集人口学特征、生活卫生习惯及宫颈病变相关信息,并采集宫颈脱落细胞和宫颈活检组织,检测HPV16的感染、hnRNP E2、HPV16 E2和E6的蛋白表达水平。根据NC组的hnRNP E2、HPV16 E2、E6蛋白表达量及E2/E6比值的M值,将研究对象分为高、低表达组/比值组,采用多因素logistic回归模型分析HPV16早期基因E2和E6、hnRNP E2与宫颈癌变的关联,并应用广义多因子降维模型(GMDR)评价其交互作用。结果NC、CINⅠ、CINⅡ/Ⅲ、SCC组的年龄分别为(47.00±9.07)、(47.64±7.35)、(46.37±8.67)和(51.26±8.03)岁。多因素logistic回归模型分析结果显示,HPV16 E2低表达、E6高表达及E2/E6低比值可导致CINⅡ/Ⅲ[OR(95%CI)值分别为11.11(1.63~75.56)、8.00(1.28~50.04)、9.75(1.22~77.72)]和SCC[OR(95%CI)值分别为14.22(2.11~95.88)、10.33(1.67~64.00)、12.38(1.56~97.91)]的患病风险增加;hnRNP E2低表达可导致CINⅡ/Ⅲ、SCC风险增加[OR(95%CI)值为3.35(1.39~8.10)、5.53(1.54~19.88)]。GMDR模型交互作用分析结果显示,hnRNP E2低表达、HPV16 E2低表达、HPV16 E6高表达在CINⅡ/Ⅲ和SCC组均存在交互作用(P值均<0.05)。结论HPV16早期基因的异常表达和hnRNP E2低表达均可能增加宫颈癌变的发病风险,且在宫颈癌变的发生发展中存在交互作用。
Objective To investigate the role of human papillomavirus(HPV)16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein(hnRNP)E2 and their interaction effects in the progression of the cervical cancer.Methods Women with normal cervix(NC),low cervical intraepithelial neoplasia(CINⅠ)and high cervical intraepithelial neoplasia(CINⅡ/Ⅲ)from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014,and patients with cervical squamous cell carcinoma(SCC)treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study.There were 257 participants,about 67 NC cases(26.07%),69 CINⅠcases(26.85%),68 CINⅡ/Ⅲcases(26.46%),and 53 SCC cases(20.62%),respectively.The information of demographic characteristics,life health habits and cervical lesions were collected by using the structured questionnaire.Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2,HPV16 E2 and E6.According to the median-value of the protein expression levels of hnRNP E2,HPV16 E2 and E6 and E2/E6 ratio in the NC group,the study participants were divided into the high and low expression groups/ratio groups.The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6,hnRNP E2 and cervical cancer.The interaction effect was analyzed by using the generalized multifactor dimensionality reduction(GMDR)model.Results The ages of NC,CINⅠ,CINⅡ/Ⅲand SCC groups were(47.00±9.07),(47.64±7.35),(46.37±8.67)and(51.26±8.03)years old,respectively.The multivariate logistic regression model analysis showed that the HPV16 E2 low expression,E6 high expression and E2/E6 low ratio could increase the risk of CINⅡ/Ⅲ,about OR(95%CI)values 11.11(1.63-75.56),8.00(1.28-50.04),and 9.75(1.22-77.72),respectively and SCC,about OR(95%CI)values 14.22(2.11-95.88),10.33(1.67-64.00),and 12.38(1.56-97.91),respectively.The hnRNP E2 low express
作者
高雯
丁玲
宋志超
冯美娟
刘春亮
李小雪
宋丽
吕元婧
王金桃
Gao Wen;Ding Ling;Song Zhichao;Feng Meijuan;Liu Chunliang;Li Xiaoxue;Song Li;Lyu Yuanjing;Wang Jintao(Department of Epidemiology,School of Public Health,Shanxi Medical University,Taiyuan 030001,China)
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2020年第1期92-98,共7页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金(81872705、81703313、81473060)
国家卫生和计划生育委员会公益性行业科研专项项目(201402010)。
关键词
人乳头瘤病毒16
子宫肿瘤
核糖核蛋白类
核不均一
交互效应
Human papillomavirus 16
Uterine neoplasms
Heterogeneous-nuclear ribonucleoproteins
Interaction effect
