| 子宫颈病变中CADM1、DAPK及RARB基因的甲基化状态 |
| 投稿时间：2017-09-26 修订日期：2017-09-28 点此下载全文 |
| 引用本文：徐彩炎,张为远,张淞文,武明辉.子宫颈病变中CADM1、DAPK及RARB基因的甲基化状态[J].医学研究杂志,2017,46(12):108-111 |
| DOI：
10.11969/j.issn.1673-548X.2017.12.027 |
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| 基金项目:北京市科委重大科研项目（D0906008040491） |
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| 中文摘要:目的 了解基因启动子的甲基化在宫颈癌发生、发展过程中的模式，为筛选和调整一个能用于诊断宫颈刮片标本中宫颈高度病变及宫颈癌的诊断标志物提供依据。方法 利用实时定量甲基特异性PCR （QMSP）分析CADM1、DAPK及RARB 3个基因启动子在宫颈病变组织中的甲基化状态。样本包括石蜡包埋正常宫颈组织20例，CIN1 40例，CIN2 40例，CIN3 18例及宫颈癌3例。同时用导流杂交法检测标本中HPV亚型。结果 CADM1及RARB两个基因的甲基化水平及甲基化阳性率都随着标本的恶性度增加而增加，在各组样本中差异有统计学意义（P<0.05）。DAPK基因的甲基化在各组样本中处于低水平，各组样本中差异无统计学意义（P>0.05）。CADM1/RARB组合敏感度、特异性最高，为82.0%及70.0%。基因甲基化水平与HPV亚型及年龄无关。结论 CADM1及RARB基因甲基化程度随宫颈病变增加而增加，两者联合检测可有效区分LSIL和HSIL病变。 |
| 中文关键词:甲基化 宫颈上皮内瘤变 |
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| Promoter Methylation of CADM1, DAPK and RARB Genes in Cervical Neoplasia |
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| Abstract:Objective To examined whether DNA methylation changes might be used as markers of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).Methods We used quantitative methylation specific PCR(QMSP) to analyze promoter hypermethylation of 3 genes, CADM1, DAPK and RARB, in 121 paraffin embedded tissue specimens collected during the previously studies of Beijing women, including normal cervix (n=20),CIN1 (n=40),CIN2 (n=40), CIN3 (n=18) and cervical cancers(n=3).Results For genes CADM1 and RARB, the level and frequency of hypermethylation increased statistically significantly with increasing severity of neoplasia present in the cervical biopsy (P<0.05 for each). The best panel of hypermethylated genes included CADM1 or RARB. At least one of the three genes was hypermethylated in 72.2% of samples with CIN3/CIS and in 100% of samples with CC but in only 5% to 30% of samples with CIN1 or less. Detection of the CADM1 or RARB hypermethylated gene would reveal histologically confirmed CIN2 or worse with a sensitivity of 82.0% and a specificity of 70.0%.HPV type and age has no influence on overall level and frequency of promoter methylation.Conclusion Aberrant promoter methylation analysis on exfoliated cell samples is a potential diagnostic tool for cervical cancer screening that potentially may be used alone or in conjunction with cytology and/or human papillomavirus testing. |
| keywords:Methylation Cervical intraepithelial neoplasia |
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