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【文献翻译】DNA甲基化分析检测高级别宫颈上皮内瘤变(CIN2+)的应用:一项系统综述和meta分析

No.1

背景

我们针对罹患高级别宫颈上皮内瘤变(CIN2+)的女性中DNA甲基化情况,进行了meta分析。

To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+).

No.2

方法

搜索Medline和Embase数据库获取用于研究甲基化标志物对比组织学终点所需资料。CIN2+的总灵敏度、特异度和阳性预测值(positive predictive value, PPV)来源于双变量模型。通过随机效应模型汇总比较了甲基化相对于细胞学和HPV16/18基因分型对CIN2+检测的相对灵敏度和特异度。

Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models.

No.3

结果

在43个研究中共16336名女性提供了有关基因(CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1)和HPV16 (L1/L2)的数据。大多数研究(81%)通过HR-HPV阳性和异常细胞学结果评估DNA甲基化的作用。总CIN2+和CIN3+的患病率分别为36.7%和21.5%。设定特异度为70%,甲基化分析对于CIN2+和CIN3+的灵敏度分别为68.6% (95% CI: 62.9–73.8)和71.1% (95% CI: 65.7–76.0),对于CIN2+和CIN3+的阳性预测值分别为53.4% (95% CI: 44.4–62.1) 和 35.0% (95% CI: 28.9–41.6)。在HR-HPV阳性女性中,相较于ASCUS或者ASCUS+和HPV16/18型,甲基化分析对于CIN2+相对灵敏度分别为0.81 (95% CI: 0.63–1.04)和1.22 (95% CI: 1.05–1.42),相对特异度则分别为1.25 (95% CI: 0.99–1.59) 和1.03 (95% CI: 0.94–1.13)。

Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9–73.8) and 71.1% (95% CI: 65.7–76.0) and PPV were 53.4% (95% CI: 44.4–62.1) and 35.0% (95% CI: 28.9–41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63–1.04) and 1.22 (95% CI: 1.05–1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99–1.59) and 1.03 (95% CI: 0.94–1.13), respectively.

文献筛选流程。

No.4

结论

相比≤CIN1(即LSIL及以下)的情况,DNA甲基化在CIN2+和CIN3+中的比例显著升高。作为分类检测,DNA甲基化相较于细胞学ASCUS+有更高的特异度,相较于HPV16/18基因分型有更高的灵敏度。

DNA methylation is significantly higher in CIN2+ and CIN3+ compared to ≤CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping.

译者的话

表观遗传学在肿瘤发生中的作用逐渐受到人们的重视,其主要表现形式有DNA 甲基化、组蛋白修饰、基因组印记、母体效应及RNA 编辑等。DNA 甲基化是重要的表观遗传学修饰形式,抑癌基因启动子区CpG 岛的高甲基化是导致抑癌基因失活的一个重要机制。DNA 甲基化异常在宫颈癌发生、发展、早期诊治及预后判断方面具有重要作用,作为宫颈癌筛查的一个标志物,DNA甲基化的应用还在探索阶段,尚未被广泛用于临床。

参考文献

Kelly H. Performance of DNA methylation assays for detection of high- grade cervical intraepithelial neoplasia (CIN2 +): a systematic review and meta-analysis. Br J Cancer. 2019;(March).

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本文系“守护女性宫颈健康”原创

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撰稿 | 陈丹

编辑 | 刘硕子

封面图片 | 赵大志

责任编辑 | 江星元

审稿 | 江路

审核 | 陶霞

声明:该文观点仅代表作者本人,搜狐号系信息发布平台,搜狐仅提供信息存储空间服务。

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