人乳头瘤病毒16 E2、E6癌基因在子宫颈癌中的表达及E2缺失分析

Analysis on the expression of human papillomavirus type 16 E2 and E6 oncogenes and disruption of E2 in cervical cancer

目的探讨人乳头瘤病毒(HPV)16型E2、E6癌基因的表达及含量变化在子宫颈癌发生中的作用,以及E2基因的缺失与子宫颈病变的关系。方法收集山西省肿瘤医院经病理学确诊的141例子宫颈癌新发病例作为病例组,同时选择在同一医院住院、经组织病理学确诊的137例子宫肌瘤患者为良性肿瘤对照组,从社区妇科体检的1582名妇女中随机抽取129名妇女为健康对照组。利用多重PCR对从子宫颈组织和脱落细胞中提取的DNA进行HPV16 E2、E6基因扩增,在VILBER凝胶成像仪上利用Bio-1D++软件分析E2、E6基因的相对含量。结果HPV16 E6阳性率在子宫颈癌组、子宫肌瘤组和健康对照组分别为46.8%、24.1%和2.3%,HPV16 E2阳性率分别为36.2%、19.0%和0.0%,差异均有统计学意义。子宫颈癌组和子宫肌瘤组中E2缺失率分别为22.73%和21.21%,健康对照组未检出E2阳性者。HPV16 E6和E2含量均为病例组高于对照组,在子宫颈癌组内E6含量明显高于E2(t=2.70,P=0.009),两者的比值为1.24。结论子宫颈癌患者HPV16 E2、E6癌基因的阳性表达率和表达量均高于子宫肌瘤患者和健康妇女,E6癌基因的高表达在子宫颈癌发生中起重要作用,而E2基因的缺失在子宫颈癌变过程中可能发挥着不可忽视的作用。

Objective To evaluate the roles of expression and early protein E2 and E6 load of human papillomavirus type 16 （HPV16） on cervical cancer in order to explore the relation between disruption of E2 and development of cervical cancer. Methods A case-control study was conducted, including 141 cervical cancer patients as cases who had been diagnosed by cytological approaches and histological approaches in Shanxi province Tumor Hospital, China. Two type of controls including 137 hospital controls with hysteromyoma by cytology or histology and eligible 129 controls from 1582 healthy women in the community who took part in community-organized physical examination with neither CIN2-3 nor invasive cancer, nor other gynecologic diseases were recruited. HPV16 E2 and E6 oncogenes were detected by multiple polymerase chain reaction （multi-PCR）. The levels of E2 and E6 were analyzed used Bio-lD ＋ ＋ software provided by VILBER pattern formatter. Results The positive rates of HPV16 E6 in cancer cases （46.8 % ） were significantly higher than that in hysteromyoma group （24.1% ） or healthy control group （2.3 % ） and accounted for 2.77 of OR （95 % CI： 1.66-4.63） and 36.96 of OR （95 % CI ： 11.22-121.71） respectively. The expressions and loads of HPV16 E6 and E2 in cases were significantly higher than that in two control groups. Meanwhile, the expression or level of E6 was higher than that of E2 in each group. Disruption rate of E2 was 22.73 % and the ratio of E6 to E2 was 1.24 in cervical cancer group. Conclusion The positive rates and levels of HPV16 E6 or E2 found in cervical cancer were higher than that in hysteromyoma and healthy women. High expression of E6 and disruption of E2 might play an important role in the development of HPV-induced cervical cancer.