Differentially hypomethylated cell-free DNA and coronary collateral circulation

Clinical Epigenetics

卷:14

Research

Jongseong Ahn¹  Duhee Bang¹  Sang-Hak Lee²  Sunghoon Heo³  Soo-jin Ahn⁴ 

[1] Department of Chemistry, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, 03722, Seoul, Korea;

[2] Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, 03722, Seoul, Korea;Pohang University of Science and Technology (POSTECH), Pohang, Korea;

[3] IMBdx, Seoul, Korea;

[4] Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Korea;

关键词: DNA methylation;    Coronary artery disease;    Cell-free DNA;    Differentially methylated regions;    Random forest;    Biomarkers;   

DOI  :  10.1186/s13148-022-01349-w

 received in 2022-06-08, accepted in 2022-10-02,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronary collateral circulation (CCC).ResultIn this case–control study, clinical and angiographic data were obtained from 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted from the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions from which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Through random forest preparation process, 256 differentially methylated region (DMR) candidates showing strong association with CCC were selected. A random forest classifier was then constructed, and the area under the curve of the receiver operating characteristic curve indicated an appropriate predictive function for CCC. Finally, 20 DMRs were identified to have significantly different AMF values between the good and poor CCC groups. Particularly, the good CCC group exhibited hypomethylated DMRs. Pathway analysis revealed five pathways, including TGF-beta signaling, to be associated with good CCC.ConclusionThese data have demonstrated that differential hypomethylation was identified in dozens of cfDNA regions in patients with good CCC. Our results support the clinical utility of noninvasively obtained epigenetic signatures for predicting collateral circulation in patients with vascular diseases.

【 授权许可】

CC BY   
© The Author(s) 2022

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