北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学临床肿瘤学院  > 肿瘤外科  > 期刊论文
学科主题: 临床医学
题名:
Large-Scale Characterization of DNA Methylation Changes in Human Gastric Carcinomas with and without Metastasis
作者: Liu, Zhaojun1; Zhang, Jun1,2; Gao, Yanhong1; Pei, Lirong3; Zhou, Jing1; Gu, Liankun1; Zhang, Lianhai4; Zhu, Budong5; Hattori, Naoko6; Ji, Jiafu4; Yuasa, Yasuhito7; Kim, Wooho8; Ushijima, Toshikazu6; Shi, Huidong3; Deng, Dajun1
刊名: CLINICAL CANCER RESEARCH
发表日期: 2014-09-01
DOI: 10.1158/1078-0432.CCR-13-3380
卷: 20, 期:17, 页:4598-4612
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: SERUM RESPONSE FACTOR ; TUMOR-SUPPRESSOR ; BREAST-CANCER ; CARDIA CANCER ; EXPRESSION ; GENE ; IDENTIFICATION ; GFR-ALPHA-1 ; GENOME ; CELLS
英文摘要:

Purpose: Metastasis is the leading cause of death for gastric carcinoma. An epigenetic biomarker panel for predicting gastric carcinoma metastasis could have significant clinical impact on the care of patients with gastric carcinoma. The main purpose of this study is to characterize the methylation differences between gastric carcinomas with and without metastasis.

Experimental Design: Genome-wide DNA methylation profiles between 4 metastatic and 4 nonmetastatic gastric carcinomas and their surgical margins (SM) were analyzed using methylated-CpG island amplification with microarray. The methylation states of 73 candidate genes were further analyzed in patients with gastric carcinoma in a discovery cohort (n = 108) using denatured high performance liquid chromatography, bisulfite-sequencing, and MethyLight. The predictive values of potential metastasis- methylation biomarkers were validated in cohorts of patients with gastric carcinoma in China (n = 330), Japan (n = 129), and Korea (n = 153).

Results: The gastric carcinoma genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared with SMs. Significant differential methylation was validated in the CpG islands of 15 genes (P < 0.05) and confirmed using bisulfite sequencing. These genes included BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Methylation changes of GFRA1, SRF, and ZNF382 resulted in up-or downregulation of their transcription. Most importantly, the prevalence of GFRA1, SRF, and ZNF382 methylation alterations was consistently and coordinately associated with gastric carcinoma metastasis and the patients′ overall survival throughout discovery and validation cohorts in China, Japan, and Korea.

Conclusion: Methylation changes of GFRA1, SRF, and ZNF382 may be a potential biomarker set for prediction of gastric carcinoma metastasis. (C) 2014 AACR.

语种: 英语
所属项目编号: 30921140311 ; 31261140372 ; 2011CB504201 ; 2010CB529300 ; CA 134304
项目资助者: Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; U.S. NIH
WOS记录号: WOS:000341835500020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64585
Appears in Collections:北京大学临床肿瘤学院_肿瘤外科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Shihezi Univ, Sch Med, Shihezi, Peoples R China
2.Natl Canc Ctr, Div Epigenet, Chuo Ku, Tokyo, Japan
3.Peking Univ, Canc Hosp & Inst, Div Etiol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
4.Georgia Regents Univ, GRU Canc Ctr, Augusta, GA USA
5.Peking Univ, Canc Hosp & Inst, Dept Surg, Beijing 100142, Peoples R China
6.Peking Univ, Canc Hosp & Inst, Dept Oncol, Beijing 100142, Peoples R China
7.Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo, Japan
8.Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea

Recommended Citation:
Liu, Zhaojun,Zhang, Jun,Gao, Yanhong,et al. Large-Scale Characterization of DNA Methylation Changes in Human Gastric Carcinomas with and without Metastasis[J]. CLINICAL CANCER RESEARCH,2014,20(17):4598-4612.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Liu, Zhaojun]'s Articles
[Zhang, Jun]'s Articles
[Gao, Yanhong]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Liu, Zhaojun]‘s Articles
[Zhang, Jun]‘s Articles
[Gao, Yanhong]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace