DNA 5-Hydroxymethylcytosines from Cell-free Circulating DNA as Diagnostic Biomarkers for Human Cancers
| Autor: | Taiping Zhang, Guifang Jia, Quan Liao, Fang Yuan, Jun Hong, Yupei Zhao, Menghua Dai, Luchun Hua, Yanqun Song, Yuanqiang Dong, Ziwen Liu, Jun Zhang, Ge Chen, Diannan Xu, Wei Zhang, Lei You, Jie Liu, Wanwei Zheng, Zhongguang Luo, Ji Nie, Yaping Wang, Shulin Yu, Marc Bissonnette, Xingyu Lu, Katherine Meckel, Fen Luo, Ming Cui, Peng Wang, Han-Kun Hao, Xiaoping Qian, Lian-Huan Wei, Xin-Xiang Zhang, Wenshuai Li, Chuan He, Sarbani Adhikari, Jianping Shi, Zhang Xu |
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| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
biology Bioinformatics medicine.disease 3. Good health Chromatin 03 medical and health sciences chemistry.chemical_compound genomic DNA 0302 clinical medicine Histone chemistry 030220 oncology & carcinogenesis Gene expression biology.protein Cancer research medicine Human genome Epigenetics Thyroid cancer DNA 030304 developmental biology |
| DOI: | 10.1101/163204 |
| Popis: | DNA modifications such as 5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC) are epigenetic marks known to affect global gene expression in mammals(1, 2). 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(3), we report here genome-wide 5hmC profiling in circulating cell-free DNA (cfDNA) and in genomic DNA of paired tumor/adjacent tissues collected from a cohort of 90 healthy individuals and 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver, or thyroid cancer. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures in cfDNA were identified with specificity for different cancers. 5hmC-based biomarkers of circulating cfDNA demonstrated highly accurate predictive value for patients with colorectal and gastric cancers versus healthy controls, superior to conventional biomarkers, and comparable to 5hmC biomarkers from tissue biopsies. This new strategy could lead to the development of effective blood-based, minimally-invasive cancer diagnosis and prognosis approaches. |
| Databáze: | OpenAIRE |
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