DNMT3A/3B overexpression might be correlated with poor patient survival, hypermethylation and low expression of ESR1/PGR in endometrioid carcinoma: an analysis of The Cancer Genome Atlas

作     者：Dan He Xiao Wang Yan Zhang Jian Zhao Rui Han Ying Dong He Dan;Wang Xiao;Zhang Yan;Zhao Jian;Han Rui;Dong Ying

作者机构：Department of PathologyPeking University First HospitalBeijing 100034China Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Gynecology and ObstetricsPeking University First HospitalBeijing 100034China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第2期

页      面：161-170页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：a grant from the National Natural Science Foundation of Ghina (No.81360381) 

主　　题：DNA (cytosine-5)-methyltransferase 3A/3B estrogens receptor Progesterone receptor Endometrial carcinoma The Cancer Genome Atlas 

摘      要：Background:DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial ***1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain ***, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied *** aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR ***:The clinicopathologic information and RNA-Seq expression data of DNMT3A/3B of 544 endometrial cancers were derived from The Cancer Genome Atlas (TCGA) uterine cancer cohort in May ***-Seq level of DNMT3A/3B was compared between these clinicopathologic factors with t-test or one-way analysis of ***:DNMT3A/3B was overexpressed in endometrioid carcinoma (EEC) and was even higher in non-endometrioid carcinoma (NEEC) (DNMT3A, EEC ***:37.6% vs.69.9%, t=-7.440, P0.001;DNMT3B, EEC ***:42.4% vs.72.8 %, t=-6.897, P0.001).In EEC, DNMT3A overexpression was significantly correlated with the hypermethylation and low expression of the ESR1 and PGR (P0.05).The same trend was observed in the DNMT3B overexpression *** the ESR1/PGR low-expression subgroups, as much as 83.1% of ESR1 and 59.5% of PGR were hypermethylated, which was significantly greater than the ESR1/PGR high-expression subgroups (31.3% and 11.9%, respectively).However, the above phenomena were absent in NEEC, while DNMT3A/3B overexpression, ESR1/PGR hypermethylation, and low ER/PR expression occurred much more *** univariate analysis, DNMT3A/3B overexpressions were significantly correlated with worse *** multivariate analysis, only DNMT3A was an independent predictor o