5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers

被引：271

作者：

Li, Wenshuai ^{[1
]}

Zhang, Xu ^{[2
]}

Lu, Xingyu ^{[3
,4
,5
]}

You, Lei ^{[6
]}

Song, Yanqun ^{[5
]}

Luo, Zhongguang ^{[1
]}

Zhang, Jun ^{[1
]}

Nie, Ji ^{[3
,4
]}

Zheng, Wanwei ^{[1
]}

Xu, Diannan ^{[1
]}

Wang, Yaping ^{[7
]}

Dong, Yuanqiang ^{[7
]}

Yu, Shulin ^{[8
]}

Hong, Jun ^{[7
]}

Shi, Jianping ^{[9
]}

Hao, Hankun ^{[7
]}

Luo, Fen ^{[7
]}

Hua, Luchun ^{[7
]}

Wang, Peng ^{[8
]}

Qian, Xiaoping ^{[10
]}

Yuan, Fang ^{[11
,12
]}

Wei, Lianhuan ^{[12
]}

Cui, Ming ^{[6
]}

Zhang, Taiping ^{[6
]}

Liao, Quan ^{[6
]}

Dai, Menghua ^{[6
]}

Liu, Ziwen ^{[6
]}

Chen, Ge ^{[6
]}

Meckel, Katherine ^{[13
]}

Adhikari, Sarbani ^{[13
]}

Jia, Guifang ^{[12
,14
]}

Bissonnette, Marc B. ^{[13
]}

Zhang, Xinxiang ^{[11
,12
]}

Zhao, Yupei ^{[6
]}

Zhang, Wei ^{[15
,16
]}

He, Chuan ^{[3
,4
,11
]}

Liu, Jie ^{[1
,17
]}

机构：

[1] Fudan Univ, Huashan Hosp, Dept Digest Dis, Shanghai 200040, Peoples R China

[2] Univ Illinois, Sect Hematol Oncol, Dept Med, Chicago, IL 60612 USA

[3] Univ Chicago, Howard Hughes Med Inst, Dept Chem, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[4] Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, Chicago, IL 60637 USA

[5] Shanghai Epican Genetech Co Ltd, Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China

[6] Chinese Acad Med Sci, Dept Gen Surg, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China

[7] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China

[8] Fudan Univ, Shanghai Canc Ctr, Dept Integrat Oncol, Shanghai 200032, Peoples R China

[9] Fudan Univ, Pudong Hosp, Dept Digest Dis, Shanghai 201399, Peoples R China

[10] Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Dept Oncol, Nanjing 210008, Jiangsu, Peoples R China

[11] Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem, Beijing 100871, Peoples R China

[12] Peking Univ, Key Lab Bioorgan Chem & Mol Engn, Minist Educ, Beijing 100871, Peoples R China

[13] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[14] Peking Univ, Coll Chem & Mol Engn, Struct & Funct Biomol Ctr, Dept Chem Biol, Beijing 100871, Peoples R China

[15] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA

[16] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

[17] Fudan Univ, Inst Biomed Sci, State Key Lab Genet Engn, Dept Immunol, Shanghai 200433, Peoples R China

来源：

CELL RESEARCH | 2017年 / 27卷 / 10期

基金：

美国国家卫生研究院;

关键词：

hydroxymethylcytosine; liquid biopsy; circulating cell-free DNA; cancer biomarker; 5hmC-Seal; GENE-EXPRESSION; TET PROTEINS; 5-METHYLCYTOSINE; PLASMA; 5-FORMYLCYTOSINE; HYDROXYLATION; CONVERSION; DISCOVERY; PATHS;

D O I：

10.1038/cr.2017.121

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.

引用

页码：1243 / 1257

页数：15

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