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[人乳头瘤病毒16型的不均一核糖核蛋白E1及早期基因E2和E6及其相互作用对宫颈癌发生的影响]

[Effects of hnRNP E1 and both early genes E2 and E6 of HPV16 together with their interactions on cervical carcinogenesis].

作者信息

Lyu Y J, Ding L, Li Q L, Li L, Wang M, Han Y, Wang J T

机构信息

Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2019 Apr 10;40(4):466-470. doi: 10.3760/cma.j.issn.0254-6450.2019.04.018.

Abstract

To explore the effects of hnRNP E1 and both early genes E2 and E6 of HPV16 as well as their interactions in the progression of cervical carcinogenesis. Subjects of this study included 56 women with normal cervix (NC), 58 patients with low-grade cervical intraepithelial neoplasm (CINⅠ) and 50 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ) who were all recruited from the 'Cervical Lesions Study Cohort Project' in Jiexiu of Shanxi province from June to September, 2014. Another 40 patients with cervical squamous cell carcinoma (SCC) were from the Shanxi Tumor Hospital during the same period. Information related to cervical lesions were collected, using a structured questionnaire, with cervical tissues and cervical exfoliated cells gathered from all the participants. HPV infection was detected by flow-through hybridization, while the levels of expression on hnRNP E1, HPV16 E2 and E6 protein were measured by Western Blot. Kruskal-Wallis test, (2) test, trend (2) test were analyzed by SPSS 22.0 software, while interaction was evaluated by generalized multifactor dimensionality reduction (GMDR). The overall infection rates of HPV16 related to CINⅠ (15.52, 9/58), CINⅡ/Ⅲ (40.00, 20/50) and SCC (67.50, 27/40) groups were all higher than that of the NC group (8.93, 5/56) and with an increasing trend on the severity of cervical lesions (trend (2)=43.613, <0.001). The levels of expression on hnRNP E1 protein were significantly different in the groups with different cervical lesions (=9.98, =0.019), showing a decreasing trend with the severity of cervical lesions (trend (2)=9.495, =0.002). The levels of expression on HPV16 E2 (=16.20, =0.001) and HPV16 E6 (=15.44, =0.001) were significantly different in groups with different cervical lesions. Results of GMDR showed that the best interaction model in both groups of CINⅡ/Ⅲ and SCC appeared as hnRNP E1 low expression, HPV16 E2 low expression and HPV16 E6 high expression. However, no similar interaction was seen in CINⅠ (>0.05). Both low expressions of hnRNP E1 and abnormal expression of HPV16 E2 and E6 could increase the risk of high-grade CIN and cervical cancer. It seemed that they might have an important synergistic effect on the progression of cervical cancer.

摘要

探讨异质性核糖核蛋白E1(hnRNP E1)、人乳头瘤病毒16型(HPV16)早期基因E2和E6及其相互作用在子宫颈癌发生发展中的作用。本研究对象包括56例宫颈正常(NC)女性、58例低度宫颈上皮内瘤变(CINⅠ)患者和50例高度宫颈上皮内瘤变(CINⅡ/Ⅲ)患者,均来自2014年6月至9月山西省介休市的“宫颈病变研究队列项目”。另外40例宫颈鳞状细胞癌(SCC)患者同期来自山西省肿瘤医院。采用结构化问卷收集与宫颈病变相关的信息,并采集所有参与者的宫颈组织和宫颈脱落细胞。采用流式杂交法检测HPV感染,采用蛋白质免疫印迹法检测hnRNP E1、HPV16 E2和E6蛋白的表达水平。采用SPSS 22.0软件进行Kruskal-Wallis检验、卡方检验、趋势卡方检验,采用广义多因素降维法(GMDR)评估相互作用。HPV16在CINⅠ组(15.52,9/58)、CINⅡ/Ⅲ组(40.00,20/50)和SCC组(67.50,27/40)的总体感染率均高于NC组(8.93,5/56),且随着宫颈病变严重程度增加呈上升趋势(趋势卡方检验=43.613,P<0.001)。hnRNP E1蛋白表达水平在不同宫颈病变组间差异有统计学意义(F=9.98,P=0.019),且随着宫颈病变严重程度增加呈下降趋势(趋势卡方检验=9.495,P=0.002)。HPV16 E2(F=16.20,P=0.001)和HPV16 E6(F=15.44,P=0.001)的表达水平在不同宫颈病变组间差异有统计学意义。GMDR结果显示,CINⅡ/Ⅲ组和SCC组的最佳相互作用模型均为hnRNP E1低表达、HPV16 E2低表达和HPV16 E6高表达。然而,CINⅠ组未发现类似相互作用(P>0.05)。hnRNP E1低表达以及HPV16 E2和E6异常表达均可能增加高级别CIN和宫颈癌发生风险。它们似乎可能在宫颈癌进展过程中发挥重要协同作用。

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