hnRNP K在宫颈上皮内瘤样变中的作用及其与HPV16交互效应

摘要

目的 探讨hnRNPK与HPV16感染在宫颈上皮内瘤样变(CIN)中的作用及其交互效应.方法 选取2014年6月至2015年6月在山西省介休市建立的社区队列中经病理学确诊的正常宫颈(NC)女性67例和CIN患者137例(CIN Ⅰ患者69例、CINⅡ/Ⅲ患者68例)为研究对象.采用结构式问卷收集研究对象人口学资料及宫颈病变相关因素的基础上,采集宫颈脱落细胞和宫颈活检或手术组织,应用分子导流杂交法检测HPV16感染状况,并采用Western blot技术检测宫颈组织中hnRNPK蛋白表达水平.采用SPSS 23.0软件对资料进行整理分析,研究对象的人口学特征、相关因素、hnRNPK蛋白和HPV16感染在NC组、CIN Ⅰ和CINⅡ/Ⅲ组的差异通过x2检验、趋势x2检验、Kruskal-Wallis H检验进行比较;hnRNPK蛋白表达量的组间两两多重比较采用Bonferroni法;采用非条件logistic回归模型计算hnRNPK蛋白、HPV16感染与CIN的关联强度OR值及其95％CI,采用相加交互模型及交互效应指标评价hnRNP K蛋白和HPV16感染两因素在CIN中的交互效应.结果 CINⅡ/Ⅲ组HPV16感染率(41.2％)高于NC(10.4％)、CIN Ⅰ (14.5％),差异有统计学意义(P＜0.001),且随着CIN程度加重,HPV16的感染率呈上升趋势(趋势x2=18.512).hnRNPK蛋白表达量在NC组、CIN Ⅰ组和CINⅡ/Ⅲ组间差异有统计学意义(H=48.138,P＜0.001),且随着C1N程度加重呈上升趋势(趋势x2=21.765,P＜0.001).交互效应分析显示,hnRNPK蛋白高表达与HPV16感染在CINⅡ/Ⅲ组存在正相加交互作用(API=0.639,95％CI:0.083～1.196),在CIN Ⅰ组尚未发现存在类似交互作用.结论 hnRNP K蛋白高表达、HPV16感染均可能增加CIN的发生风险,且在高度CIN发生中存在正相加交互作用.%Objective To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavims 16 (HPV16) on cervical intraepithelial neoplasia (CIN).Methods The participants included 67 women with normal cervix (NC),69 women with CIN Ⅰ and 68 women with CIN Ⅱ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province,from June 2014 to June 2015.A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions.Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected.The infection status of HPV16 was detected by flow-through hybridization.The protein expression levels of hnRNP K were evaluated by Western blot.SPSS 23.0 software was used to collate and analyze the data.To study the differences in demographic characteristics,related factors,hnRNP K protein and HPV16 infection among NC,CIN Ⅰ and CIN Ⅱ / Ⅲ groups,X2 test,trend x2 test,and Kruskal-Wallis H test were conducted.Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method.The OR and its 95％CI of hnRNP K,HPV16 and CIN were calculated by using the unconditional logistic regression models.Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators.Results HPV16 infection rates were 10.4％ in women with normal cervix,14.5％ in women with CIN Ⅰ and 41.2％ in women with CIN Ⅱ/Ⅲ,respectively.The differences among three groups were significant (P＜0.001).Moreover,the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend x2=18.512,P＜0.001).The differences in protein expression of hnRNP K among three groups were significant (H=48.138,P＜0.001) and the expressionincreased with the development of cervical lesionss (trend x2=21.765,P＜0.001).Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CIN Ⅱ/Ⅲ group compared with normal group (API=0.639,95％CI:0.083-1.196).In contrast,no such additive effect was found in CIN Ⅰ group.Conclusions HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia.There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CIN Ⅰ/Ⅲ.