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 QianFang 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 journalArticlepeer-review

113 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of '5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers'. Together they form a unique fingerprint.

Cite this