| Title | 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease |
| Authors | Dong, Chaoran Chen, Jiemei Zheng, Jilin Liang, Yiming Yu, Tao Liu, Yupeng Gao, Feng Long, Jie Chen, Hangyu Zhu, Qianhui He, Zilong Hu, Songnian He, Chuan Lin, Jian Tang, Yida Zhu, Haibo |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Bioact Subst & Funct Nat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Inst Mat Med, Xian Nong Tan St 1, Beijing 100050, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Cardiovasc Dis, Natl Ctr Cardiovasc Dis, Dept Cardiol,Coronary Heart Dis Ctr,Fu Wai Hosp, 167 Beilishi Rd, Beijing 100037, Peoples R China Peking Univ, Coll Chem & Mol Engn, Innovat Ctr Genom, 5 Yiheyuan Rd, Beijing 100871, Peoples R China Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China Univ Chinese Acad Sci, Beijing, Peoples R China Univ Chicago, Howard Hughes Med Inst, Dept Chem, Dept Biochem & Mol Biol, 5841 S Maryland Ave, Chicago, IL 60637 USA |
| Keywords | TET2 REGULATOR METHYLATION PERFORMANCE EXPRESSION MORTALITY ELEMENTS MARKERS |
| Issue Date | 21-Jan-2020 |
| Publisher | CLINICAL EPIGENETICS |
| Abstract | Background The 5-hydroxymethylcytosine (5hmC) DNA modification is an epigenetic marker involved in a range of biological processes. Its function has been studied extensively in tumors, neurodegenerative diseases, and atherosclerosis. Studies have reported that 5hmC modification is closely related to the phenotype transformation of vascular smooth muscle cells and endothelial dysfunction. However, its role in coronary artery disease (CAD) has not been fully studied. Results To investigate whether 5hmC modification correlates with CAD pathogenesis and whether 5hmC can be used as a biomarker, we used a low-input whole-genome sequencing technology based on selective chemical capture (hmC-Seal) to firstly generate the 5hmC profiles in the circulating cell-free DNA(cfDNA) of CAD patients, including stable coronary artery disease (sCAD) patients and acute myocardial infarction (AMI) patients. We detected a significant difference of 5hmC enrichment in gene bodies from CAD patients compared with normal coronary artery (NCA) individuals. Our results showed that CAD patients can be well separated from NCA individuals by 5hmC markers. The prediction performance of the model established by differentially regulated 5hmc modified genes were superior to common clinical indicators for the diagnosis of CAD (AUC = 0.93) and sCAD (AUC = 0.93). Specially, we found that 5hmC markers in cfDNA showed prediction potential for AMI (AUC = 0.95), which was superior to that of cardiac troponin I, muscle/brain creatine kinase, and myoglobin. Conclusions Our results suggest that 5hmC markers derived from cfDNA can serve as effective epigenetic biomarkers for minimally noninvasive diagnosis and prediction of CAD. |
| URI | http://hdl.handle.net/20.500.11897/586133 |
| ISSN | 1868-7075 |
| DOI | 10.1186/s13148-020-0810-2 |
| Indexed | SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
