*Department of Obstetrics and Gynecology, Tri-Service General Hospital; †Laboratory of Epigenetics and Cancer Stem Cells, and ‡Graduate Institute of Medical Sciences, National Defense Medical Center; and §Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China.
Int J Gynecol Cancer. 2014 Feb;24(2):201-9. doi: 10.1097/IGC.0000000000000054.
This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix.
We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing.
The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P < 0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P < 0.001).
Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582--commonly methylated in squamous cell carcinomas--which might help for AC screening.
本研究旨在探讨先前在宫颈癌鳞状细胞癌中发现的 6 个基因（LMX1A、NKX6-1、PAX1、PTPRR、SOX1 和 ZNF582）在子宫颈腺癌（AC）中的 DNA 甲基化状态。
我们通过实时定量甲基化特异性聚合酶链反应评估了 40 例 AC、23 例 AC 宫颈刮片和 67 例正常对照宫颈组织中这些基因的甲基化状态。结果通过亚硫酸氢盐焦磷酸测序进行验证。
所有 6 个基因在 AC 中的甲基化水平明显高于正常宫颈组织，尤其是 PAX1、PTPRR、SOX1 和 ZNF582。PAX1、PTPRR、SOX1 和 ZNF582 高甲基化水平对 AC 发病风险的比值比（OR）和 95%置信区间（CI）分别为 15.7（95%CI，7.0-40.6）、16.9（95%CI，7.6-43.0）、32.1（95%CI，12.1-124.3）和 25.4（95%CI，10.4-78.3）（均 P<0.001）。AC 刮片中 PAX1、PTPRR、SOX1 和 ZNF582 的甲基化指数明显高于正常对照组。PAX1、PTPRR、SOX1 和 ZNF582 这些指数对 AC 发病风险的 OR 分别为 6.2（95%CI，2.6-15.4）、12.1（95%CI，3.8-46.4）、6.2（95%CI，2.6-15.8）和 20.6（95%CI，6.9-77.5）（均 P<0.001）。
子宫颈 AC 存在 PAX1、PTPRR、SOX1 和 ZNF582 异常高的甲基化率，这些基因通常在鳞状细胞癌中甲基化，这可能有助于 AC 的筛查。
