Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1243-1257 |
| Number of pages | 15 |
| Journal | Cell Research |
| Volume | 27 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2017 |
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Keywords
- 5-hydroxymethylcytosine
- 5hmC-Seal
- cancer biomarker
- circulating cell-free DNA
- liquid biopsy
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
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5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers. / Li, Wenshuai; Zhang, Xu; Lu, Xingyu; You, Lei; Song, Yanqun; Luo, Zhongguang; Zhang, Jun; Nie, Ji; Zheng, Wanwei; Xu, Diannan; Wang, Yaping; Dong, Yuanqiang; Yu, Shulin; Hong, Jun; Shi, Jianping; Hao, Hankun; Luo, Fen; Hua, Luchun; Wang, Peng; Qian, Xiaoping; Yuan, Fang; Wei, Lianhuan; Cui, Ming; Zhang, Taiping; Liao, Quan; Dai, Menghua; Liu, Ziwen; Chen, Ge; Meckel, Katherine; Adhikari, Sarbani; Jia, Guifang; Bissonnette, Marc B.; Zhang, Xinxiang; Zhao, Yupei; Zhang, Wei; He, Chuan; Liu, Jie.
In: Cell Research, Vol. 27, No. 10, 01.10.2017, p. 1243-1257.Research output: Contribution to journal › Article
TY - JOUR
T1 - 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers
AU - Li, Wenshuai
AU - Zhang, Xu
AU - Lu, Xingyu
AU - You, Lei
AU - Song, Yanqun
AU - Luo, Zhongguang
AU - Zhang, Jun
AU - Nie, Ji
AU - Zheng, Wanwei
AU - Xu, Diannan
AU - Wang, Yaping
AU - Dong, Yuanqiang
AU - Yu, Shulin
AU - Hong, Jun
AU - Shi, Jianping
AU - Hao, Hankun
AU - Luo, Fen
AU - Hua, Luchun
AU - Wang, Peng
AU - Qian, Xiaoping
AU - Yuan, Fang
AU - Wei, Lianhuan
AU - Cui, Ming
AU - Zhang, Taiping
AU - Liao, Quan
AU - Dai, Menghua
AU - Liu, Ziwen
AU - Chen, Ge
AU - Meckel, Katherine
AU - Adhikari, Sarbani
AU - Jia, Guifang
AU - Bissonnette, Marc B.
AU - Zhang, Xinxiang
AU - Zhao, Yupei
AU - Zhang, Wei
AU - He, Chuan
AU - Liu, Jie
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - 5-hydroxymethylcytosine
KW - 5hmC-Seal
KW - cancer biomarker
KW - circulating cell-free DNA
KW - liquid biopsy
UR - http://www.scopus.com/inward/record.url?scp=85030673933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030673933&partnerID=8YFLogxK
U2 - 10.1038/cr.2017.121
DO - 10.1038/cr.2017.121
M3 - Article
VL - 27
SP - 1243
EP - 1257
JO - Cell Research
JF - Cell Research
SN - 1001-0602
IS - 10
ER -