高危型人乳头瘤病毒阳性的宫颈癌组织中L1基因甲基化水平变化及意义

摘要

Objective To observe the changes of methylation level of the long interspersed nucleotid element -1(L1)in persistent high-risk human papillomavirus ( HR-HPV) positive cervical cancer tissue and its significance .Methods Thirty tissue samples were collected in all HR-HPV infected normal cervix , cervical intraepithelial neoplasia ( CIN)Ⅰ, CINⅡ-CINⅢand cervical cancer respectively .Three CpG sites methylation levels of the L 1 of all tissues were quantitatively ana-lyzed by bisulphite conversion and pyrosequencing technology .Evaluated its diagnostic value in cervical cancer and CIN . Results The mean levels and standard deviation of the L 1 promoter methylation level of normal cervix tissue , CINⅠtis-sue, CINⅡ~Ⅲtissue and cervical cancer tissue were 0.59 ±0.053, 0.57 ±0.038, 0.56 ±0.025, 0.49 ±0.054 re-spectively.Compared the L1 promoter mean methylation level of cervical cancer tissues with other tissues , all P<0.001. Selected the cutoff value of the L 1 gene methylation level as 53 .17%, both the sensitivity and specificity to judge the prop-erty of cervical lesions were 86.70%, with the 95%confidence interval (CI) was 0.834~0.976.Conclusions The L1 gene methylation level of HR-HPV positive cervical cancer tissue decrease significantly .It helps to judge the property of cervical lesions with the L1 gene promoter methylation level of 53.17%.%目的：观察持续性高危型人乳头瘤病毒（ HR-HPV）阳性的宫颈癌组织中长散布核元件-1（ L1）基因甲基化水平变化，并探讨其意义。方法收集HR-HPV均阳性的正常宫颈组织、宫颈上皮内瘤变（ CIN） I组织、CINⅡ～Ⅲ组织及宫颈癌组织各30份。采用亚硫酸氢盐转化结合焦磷酸测序技术对所有组织DNA的L1序列3个CpG位点进行甲基化定量检测，评价其对子宫颈癌和CIN的诊断价值。结果正常宫颈组织、CIN Ⅰ组织、CINⅡ～Ⅲ组织及宫颈癌组织中L1基因平均甲基化水平分别为0．590±0．053、0．570±0．038、0．560±0．025、0．490±0．054，宫颈癌组织中L1基因平均甲基化水平与其他组织中比较，P均＜0．001。选取L1基因启动子区甲基化水平的截断值为53．17％，此时其判断宫颈病变性质的灵敏度及特异度均为86．70％。95％置信区间（CI）为0．834～0．976。结论HR-HPV阳性的宫颈癌组织中L1基因甲基化水平明显降低。 L1基因启动子区甲基化水平为53．17％时，有助于宫颈病变性质的判断。