Analysis of DNA methylation in endometrial biopsies to predict risk of Chock for endometrial cancer
Analysis of DNA methylation in endometrial biopsies to predict risk of Chock for endometrial cancer
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DOI：
10.1016/j.ygyno.2019.12.023
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发表时间：
2020-03-01
影响因子：
4.7
通讯作者：
Walther-Antonio, Marina
中科院分区：
文献类型：
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作者：
Multinu, Francesco;Chen, Jun;Walther-Antonio, Marina
Objective.目的：探讨良性子宫内膜活检（EB）标本中甲基化DNA的分析是否与子宫内膜癌（EC）的风险相关。我们确定了23名在马约诊所进行EB检查的妇女，诊断为正常（n = 14）或增生（n = 9），后来在中位间隔1年后发展为子宫内膜癌。根据良性EB的组织学（正常子宫内膜vs.子宫内膜增生不伴子宫内膜异位症）、EB日期、EB时的年龄和活检后随访时间，将病例与未发生EC的良性EB患者（对照组）1：1匹配。从福尔马林固定的石蜡包埋组织中提取的DNA进行焦磷酸测序，以确定先前在EC中报告为甲基化的4个基因（ADCYAP 1，HAND 2，MME，RASSFIA）的26个位点的启动子区域CpG的甲基化百分比。经病理学检查，23对配对的病例和对照组进行了鉴定（每组14例正常，9例增生不伴前列腺增生）。在这些病例中，从良性EB到EC的中位时间为1年（范围2天9.2年）。我们评估了4个基因内的26个CpG位点，发现所有CpG的甲基化百分比从对照到病例到EC的一致趋势。在基因水平上，病例中ADCYAPI和HAND 2的平均甲基化事件显著高于对照（分别为p = 0.015和p = 0.021）。虽然其他基因没有达到统计学显著性，但我们观察到所有基因中甲基化趋势增加。ADCYAPI和HAND 2的曲线下面积（AUC）计算（预测良性EB背景下EC的未来发展）分别为0.71（95%CI 0.55-0.88）和0.83（95%CI 0.64-1）。这项原理验证研究提供了证据，表明良性EB中的特定甲基化模式与EC的未来发展相关。(C)2019年，任作家。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Objective. To determine whether analysis of methylated DNA in benign endometrial biopsy (EB) specimens is associated with risk of endometrial cancer (EC).Methods. We identified 23 women with EBs performed at Mayo Clinic diagnosed as normal (n = 14) or hyperplasia (n = 9) and who later developed endometrial cancer after a median interval of 1 year. Cases were matched 1:1 with patients with benign EBs who did not develop EC (controls) by histology of benign EB (normal endometrium vs. endometrial hyperplasia without atypia), date of EB, age at EB, and length of post-biopsy follow-up. DNA extracted from formalin-fixed paraffin-embedded tissues underwent pyrosequencing to determine percent methylation of promoter region CpGs at 26 loci in 4 genes (ADCYAP1, HAND2, MME, RASSFIA) previously reported as methylated in EC.Results. After pathologic review, 23 matched pairs of cases and controls were identified (14 normal, 9 hyperplasia without atypia per group). Among cases, median time from benign EB to EC was 1 year (range 2 days 9.2 years). We evaluated 26 CpG sites within 4 genes and found a consistent trend of increasing percentage of methylation from control to case to EC for all CpGs. At the gene-level, mean methylation events of ADCYAPI and HAND2 in cases were significantly higher than control (p = 0.015 and p = 0.021, respectively). Though the other genes did not reach statistical significance, we observed an increased methylation trend among all genes. Area-under-curve (AUC) calculations (predicting future development of EC in the setting of benign EB) for ADCYAPI and HAND2 were 0.71 (95% CI 0.55-0.88) and 0.83 (95% Cl 0.64-1, respectively).Conclusions. This proof-of-principle study provides evidence that specific methylation patterns in benign EB correlate with future development of EC. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).