DNA methylation analysis in liquid-based cytology for cervical cancer screening
DNA methylation analysis in liquid-based cytology for cervical cancer screening
复制标题
DOI：
10.1002/ijc.24745
复制
发表时间：
2009-12-15
影响因子：
6.4
通讯作者：
Widschwendter, Martin
中科院分区：
文献类型：
--
作者：
Apostolidou, Sophia;Hadwin, Richard;Widschwendter, Martin
宫颈癌是世界范围内女性第二常见的癌症类型。宫颈细胞学检查可发现浸润前病变。目前所有可用的细胞学技术都依赖于对子宫颈脱落细胞的视觉分析。传统的细胞学筛查的改进已被提出，通过引入基于分子的标记物应用于液基细胞学（LBC），从子宫颈收集的细胞悬浮液。DNA甲基化变化发生在癌变的早期，在这些样本中鉴定合适的DNA甲基化标记物应该能够区分高度鳞状上皮内病变（HSIL）前非特异性细胞学变化和正常宫颈。为了解决这一问题，我们对HSIL细胞学病例的LBC样本的甲基化状态与匹配的正常对照进行了原理验证研究。使用28个基因的定量甲基化特异性PCR，我们发现SOX 1、HOXA 11和CAl在分析的组之间具有显著的区分性（p < 0.01）。受试者工作特征（ROC）曲线下面积（AUC）显示SOX 1、HOXA 11和CA 11甲基化可区分HSIL病例和对照，具有较高的敏感性和特异性（AUC分别为0.910、0.844和0.760）。在一个独立的集合中进一步验证了结果。这项原理验证研究是第一个在独立的病例/对照组中验证结果的研究，并提出了HOXA 11，一种对宫颈发育很重要的基因，作为LBC样本中潜在有用的DNA标记。需要在更大的队列中对这些初步估计进行进一步评估，以确认临床实用性。(C)2009年UICC
Cervical cancer is the second most common type of cancer in women worldwide. Preinvasive disease can be detected by cervical cytology. All currently available cytology technologies rely on the visual analysis of exfoliated cells from the uterine cervix. Improvement of conventional cytological screening has been proposed by the introduction of molecular-based markers applied to liquid-based cytology (LBC), the suspension of cells collected from the cervix. DNA methylation changes occur very early in carcinogenesis and identification of appropriate DNA methylation markers in such samples should be able to distinguish high-grade squamous intraepithelial lesions (HSIL) front nonspecific cytology changes and the normal cervix. To address this potential, we have undertaken a proof-of-principle study of methylation status of LBC samples from HSIL cytology cases compared against matched normal controls. Using quantitative methylation-specific PCR on 28 genes, we found SOX1, HOXA11 and CADMI to significantly discriminate between the groups analyzed (p < 0.01). Area under the receiver operating characteristic (ROC) curve (AUC) demonstrated that methylation of SOX1, HOXA11 and CADMI could discriminate between HSIL cases and controls with high sensitivity and specificity (AUC 0.910, 0.844 and 0.760, respectively). The results were further validated in an independent set. This proof-of-principle study is the first to validate the results in an independent case/control set and presents HOXA11, a gene that is important for cervical development, as a potentially useful DNA marker in LBC samples. Further assessment of these preliminary estimates will need to be performed in a larger cohort to confirm clinical utility. (C) 2009 UICC