Croes Lieselot, de Beeck Ken Op, Pauwels Patrick, Vanden Berghe Wim, Peeters Marc, Fransen Erik, Van Camp Guy
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
Oncotarget. 2017 May 9;8(19):31948-31958. doi: 10.18632/oncotarget.16654.
Identification of methylation markers that are sensitive and specific for breast cancer may improve early detection. We hypothesize that DFNA5 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death.
Statistically different levels of methylation were seen, with always very low levels in healthy breast reduction samples, very high levels in part of the adenocarcinoma samples and slightly increased levels in part of the normal tissue samples adjacent the tumor. One of the CpGs (CpG4) showed the best differentiation. A ROC curve for DFNA5 CpG4 methylation showed a sensitivity of 61.8% for the detection of breast cancer with a specificity of 100%.
We performed methylation analysis on four CpGs in the DFNA5 promoter region by bisulfite pyrosequencing on 123 primary breast adenocarcinomas and 24 healthy breast reductions. For 16 primary tumors, corresponding histological normal tissue adjacent to the tumor was available.
We conclude that DFNA5 methylation shows strong potential as a biomarker for detection of breast cancer. Slightly increased methylation in histologically normal breast tissue surrounding the tumor suggests that it may be a good early detection marker.
鉴定对乳腺癌敏感且特异的甲基化标志物可能会改善早期检测。基于DFNA5作为肿瘤抑制基因的作用及其在调控细胞死亡中的功能的有力证据，我们假设DFNA5启动子甲基化可以成为一种有价值的表观遗传生物标志物。
观察到甲基化水平存在统计学差异，在健康的乳房缩小样本中甲基化水平始终非常低，在部分腺癌样本中甲基化水平非常高，在肿瘤周围的部分正常组织样本中甲基化水平略有升高。其中一个CpG（CpG4）表现出最佳的区分能力。DFNA5 CpG4甲基化的ROC曲线显示，检测乳腺癌的灵敏度为61.8%，特异性为100%。
我们通过亚硫酸氢盐焦磷酸测序对123例原发性乳腺腺癌和24例健康乳房缩小样本的DFNA5启动子区域中的四个CpG进行了甲基化分析。对于16例原发性肿瘤，可获得与其相邻的相应组织学正常组织。
我们得出结论，DFNA5甲基化作为乳腺癌检测的生物标志物具有很强的潜力。肿瘤周围组织学正常的乳腺组织中甲基化水平略有升高表明它可能是一个良好的早期检测标志物。
