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

Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian & 17 others Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B. Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1243-1257
Number of pages15
JournalCell Research
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Tumor Biomarkers
DNA
Biomarkers
Epigenomics
Stomach Neoplasms
Colorectal Neoplasms
Neoplasms
Histone Code
5-Methylcytosine
Gene Expression
Human Genome
Liver Neoplasms
Pancreatic Neoplasms
Thyroid Neoplasms
Chromatin
5-hydroxymethylcytosine
Mammals
Genome
Technology
Biopsy

Keywords

  • 5-hydroxymethylcytosine
  • 5hmC-Seal
  • cancer biomarker
  • circulating cell-free DNA
  • liquid biopsy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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. / 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers. In: Cell Research. 2017 ; Vol. 27, No. 10. pp. 1243-1257.
@article{ea9fa4c7a21c4ad6abeca7cab6c4dafe,
title = "5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers",
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.",
keywords = "5-hydroxymethylcytosine, 5hmC-Seal, cancer biomarker, circulating cell-free DNA, liquid biopsy",
author = "Wenshuai Li and Xu Zhang and Xingyu Lu and Lei You and Yanqun Song and Zhongguang Luo and Jun Zhang and Ji Nie and Wanwei Zheng and Diannan Xu and Yaping Wang and Yuanqiang Dong and Shulin Yu and Jun Hong and Jianping Shi and Hankun Hao and Fen Luo and Luchun Hua and Peng Wang and Xiaoping Qian and Fang Yuan and Lianhuan Wei and Ming Cui and Taiping Zhang and Quan Liao and Menghua Dai and Ziwen Liu and Ge Chen and Katherine Meckel and Sarbani Adhikari and Guifang Jia and Bissonnette, {Marc B.} and Xinxiang Zhang and Yupei Zhao and Wei Zhang and Chuan He and Jie Liu",
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month = "10",
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journal = "Cell Research",
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Li, W, Zhang, X, Lu, X, You, L, Song, Y, Luo, Z, Zhang, J, Nie, J, Zheng, W, Xu, D, Wang, Y, Dong, Y, Yu, S, Hong, J, Shi, J, Hao, H, Luo, F, Hua, L, Wang, P, Qian, X, Yuan, F, Wei, L, Cui, M, Zhang, T, Liao, Q, Dai, M, Liu, Z, Chen, G, Meckel, K, Adhikari, S, Jia, G, Bissonnette, MB, Zhang, X, Zhao, Y, Zhang, W, He, C & Liu, J 2017, '5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers', Cell Research, vol. 27, no. 10, pp. 1243-1257. https://doi.org/10.1038/cr.2017.121

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 journalArticle

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

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U2 - 10.1038/cr.2017.121

DO - 10.1038/cr.2017.121

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SP - 1243

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JO - Cell Research

JF - Cell Research

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