Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
J Gynecol Oncol. 2022 Nov;33(6):e74. doi: 10.3802/jgo.2022.33.e74. Epub 2022 Aug 16.
The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile.
Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip.
Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established.
DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for , , , , , and may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.
本研究旨在基于患者的 DNA 甲基化谱，建立标准来确定对于年龄在 40 岁及以下的子宫内膜样腺癌患者，行生育力保存治疗是否安全。
对初始队列中 49 例子宫内膜癌患者的新鲜冷冻组织样本和第二队列中 31 例福尔马林固定石蜡包埋组织样本进行全基因组 DNA 甲基化分析，使用 Infinium MethylationEPIC BeadChip。
早期发病的子宫内膜癌的表观基因组聚类与广泛使用的复发风险分类相关。在低复发风险组和中、高风险组之间显示 DNA 甲基化水平差异的基因在与成纤维细胞生长因子和核因子-κB 信号相关的途径中累积。在低风险组中经常观察到 DNA 低甲基化和 的过表达。831 个标记 CpG 探针在初始和第二队列中，对低风险组患者的区分具有 >0.7 的曲线下面积值。通过组合标记 CpG 位点，建立了用于将患者分为低风险类别的七个面板，在初始和第二队列中均具有 91.3%或更高的敏感性和特异性。
使用多达 8 个 CpG 位点中的 6 个，包括、、、、、和，进行 DNA 甲基化诊断标准，可能适用于年龄在 40 岁及以下的子宫内膜癌患者的复发风险评估，无论肿瘤细胞含量如何，即使使用福尔马林固定石蜡包埋的活检或刮宫材料。
