Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles.
Prognostication of early-onset endometrioid endometrial cancer based on genome-wide DNA methylation profiles.
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DOI：
10.3802/jgo.2022.33.e74
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发表时间：
2022-11
影响因子：
3.9
通讯作者：
Kanai Y
中科院分区：
文献类型：
--
作者：
Hirano T;Arai E;Fujimoto M;Nakayama Y;Tian Y;Ito N;Makabe T;Yamagami W;Susumu N;Aoki D;Kanai Y
本研究的目的是根据 DNA 甲基化谱建立标准，表明生育力保存治疗对于 40 岁或以下患有子宫内膜样子宫内膜癌的患者是否安全。使用 Infinium MmethylationEPIC BeadChip 对来自初始队列的子宫内膜癌患者的 49 个新鲜冷冻组织样本和来自第二队列的 31 个福尔马林固定石蜡包埋的组织样本进行全基因组 DNA 甲基化分析。早发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。低复发风险类别与中高风险类别之间 DNA 甲基化水平存在差异的基因在与成纤维细胞生长因子和核因子-κB 信号传导相关的通路中积累。 DNA 低甲基化和 ZBTB38 过度表达在低风险人群中经常观察到。 831 个标记物 CpG 探针在受试者操作特征曲线上显示曲线下面积值 >0.7，用于区分属于低风险类别的患者。通过结合标记物 CpG 位点，建立了七个组，用于将患者归入低风险类别，在初始队列和第二队列中具有 91.3% 或更高的敏感性和特异性。使用 LPP、FOXO1、RNF4、EXOC6B、CCPG1、RREB1 和 ZBTB38 的 8 个 CpG 位点中最多 6 个的 DNA 甲基化诊断标准可能适用于 40 岁或以下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活检或刮宫材料。早发子宫内膜癌的 DNA 甲基化改变在成纤维细胞生长因子和核因子-κB 通路中积累，显示出较高的复发风险。 DNA 低甲基化和 ZBTB38 过度表达在低风险类别中很常见。 DNA 甲基化标准可能适用于使用活检或刮除样本进行复发风险评估。
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 ZBTB38 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 LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 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. DNA methylation alterations of early-onset endometrial cancer showing the higher recurrence risk were accumulated in the fibroblast growth factor and nuclear factor-κB pathways. DNA hypomethylation and overexpression of ZBTB38 were frequent in the low-risk category. DNA methylation criteria may be applicable for recurrence risk estimation using biopsy or curettage samples.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Fujimoto M;Arai E;Tsumura K;Yotani T;Yamada Y;Takahashi Y;Maeshima AM;Fujimoto H;Yoshida T;Kanai Y
通讯作者：
Kanai Y
影响因子：
5.7
作者：
Wen, Xianyu;Jeong, Seorin;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon
影响因子：
3.9
作者：
Erdogan B;Webb DJ
通讯作者：
Webb DJ
影响因子：
5.2
作者：
de Dieuleveult, Maud;Marchal, Claire;Miotto, Benoit
通讯作者：
Miotto, Benoit