DNA Methylation Profiling of Human Hepatocarcinogenesis

DNA甲基化 表观遗传学 生物 甲基化 CpG站点 癌症研究 差异甲基化区 分子生物学 基因表达 遗传学 基因
作者
Gabriela Hernandez‐Meza,Johann von Felden,Edgar Gonzalez‐Kozlova,Teresa García‐Lezana,Judit Peix,Anna Portela,Amanda J. Craig,Sergi Sayols,Myron Schwartz,Bojan Losic,Vincenzo Mazzaferro,Manel Esteller,Josep M. Llovet,Augusto Villanueva
出处
期刊:Hepatology [Lippincott Williams & Wilkins]
卷期号:74 (1): 183-199 被引量:60
标识
DOI:10.1002/hep.31659
摘要

Mutations in TERT (telomerase reverse transcriptase) promoter are established gatekeepers in early hepatocarcinogenesis, but little is known about other molecular alterations driving this process. Epigenetic deregulation is a critical event in early malignancies. Thus, we aimed to (1) analyze DNA methylation changes during the transition from preneoplastic lesions to early HCC (eHCC) and identify candidate epigenetic gatekeepers, and to (2) assess the prognostic potential of methylation changes in cirrhotic tissue.Methylome profiling was performed using Illumina HumanMethylation450 (485,000 cytosine-phosphateguanine, 96% of known cytosine-phosphateguanine islands), with data available for a total of 390 samples: 16 healthy liver, 139 cirrhotic tissue, 8 dysplastic nodules, and 227 HCC samples, including 40 eHCC below 2cm. A phylo-epigenetic tree derived from the Euclidean distances between differentially DNA-methylated sites (n = 421,997) revealed a gradient of methylation changes spanning healthy liver, cirrhotic tissue, dysplastic nodules, and HCC with closest proximity of dysplasia to HCC. Focusing on promoter regions, we identified epigenetic gatekeeper candidates with an increasing proportion of hypermethylated samples (beta value > 0.5) from cirrhotic tissue (<1%), to dysplastic nodules (≥25%), to eHCC (≥50%), and confirmed inverse correlation between DNA methylation and gene expression for TSPYL5 (testis-specific Y-encoded-like protein 5), KCNA3 (potassium voltage-gated channel, shaker-related subfamily, member 3), LDHB (lactate dehydrogenase B), and SPINT2 (serine peptidase inhibitor, Kunitz type 2) (all P < 0.001). Unsupervised clustering of genome-wide methylation profiles of cirrhotic tissue identified two clusters, M1 and M2, with 42% and 58% of patients, respectively, which correlates with survival (P < 0.05), independent of etiology.Genome-wide DNA-methylation profiles accurately discriminate the different histological stages of human hepatocarcinogenesis. We report on epigenetic gatekeepers in the transition between dysplastic nodules and eHCC. DNA-methylation changes in cirrhotic tissue correlate with clinical outcomes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
超级灵竹完成签到,获得积分10
1秒前
HuiHui发布了新的文献求助10
2秒前
3秒前
4秒前
香蕉觅云应助科研通管家采纳,获得10
5秒前
5秒前
汉堡包应助科研通管家采纳,获得30
6秒前
6秒前
852应助科研通管家采纳,获得10
6秒前
6秒前
顾矜应助科研通管家采纳,获得10
6秒前
6秒前
斯文败类应助科研通管家采纳,获得10
6秒前
6秒前
6秒前
水木应助科研通管家采纳,获得20
6秒前
大个应助未明的感觉采纳,获得10
8秒前
光亮的半山完成签到,获得积分10
9秒前
9秒前
10秒前
10秒前
slx发布了新的文献求助10
11秒前
Akim应助比利时光采纳,获得10
11秒前
思源应助waitingfor采纳,获得10
12秒前
12秒前
DueR完成签到,获得积分10
13秒前
清爽乐菱应助失眠的夜梦采纳,获得30
13秒前
磊磊完成签到,获得积分10
14秒前
Chelry发布了新的文献求助30
14秒前
闾丘剑封发布了新的文献求助10
14秒前
Chief完成签到,获得积分0
15秒前
mk91发布了新的文献求助10
15秒前
镇江市第一人民医院第一深情完成签到,获得积分10
16秒前
xiaoyuanbao1988完成签到,获得积分10
16秒前
qin希望应助不回首采纳,获得10
17秒前
上官若男应助不回首采纳,获得10
17秒前
科研通AI2S应助不回首采纳,获得10
17秒前
Jasper应助不回首采纳,获得10
17秒前
科研通AI5应助不回首采纳,获得10
17秒前
JamesPei应助不回首采纳,获得10
17秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989510
求助须知:如何正确求助?哪些是违规求助? 3531756
关于积分的说明 11254536
捐赠科研通 3270255
什么是DOI,文献DOI怎么找? 1804947
邀请新用户注册赠送积分活动 882113
科研通“疑难数据库(出版商)”最低求助积分说明 809176