Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism
单位：[a]Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China临床科室国家中心普外分中心普外四科（肝脏移植外科）首都医科大学附属北京友谊医院[b]Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China[c]Basecare Medical Device Co., Ltd, 218 Xinghu Road, SIP., Suzhou, Jiangsu 215001, China[d]State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China[e]Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA[f]Texas Children's Hospital, Houston, TX, USA[g]The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics, Hong Kong SAR, China
Graft-derived-cell-free DNA (Gcf-DNA) in plasma is a promising biomarker to monitor graft-rejection after liver transplantation (LTx). However, current methods of measuring Gcf-DNA have several limitations including high cost, long turnaround-time and the need to request donor's genetic information. In this study, eleven patients diagnosed with different inborn errors of metabolism (IEMs) who required living-related LTx were enrolled in order to establish a potentially useful noninvasive method to monitor graft damage. Circulating cell-free DNA (cfDNA) was extracted from plasma specimens serially collected at specific time points (day 0, day 1, day 7, day 14, day 30, day 60) after LTx. The distribution of Gcf-DNA fragment sizes was measured using sequencing read lengths and quantified by using Y-chromosome capture methodology in seven sex-mismatched recipients. In the analysis of fragment size distribution, we observed Gcf-DNA exhibited smaller fragment sizes than the recipient-cfDNA. Based on this phenomenon, two fragment sizes (105-145 bp, 160-170 bp) of the cfDNA pool were extracted to enrich Gcf-DNA. Accordingly, the ratio of short fragments to long fragments (S/L-Frag) in cfDNA was calculated. A high S/L-Frag ratio pointed towards an early trend of graft injury when compared to two routine liver function enzymes (ALT and AST) and Gcf-DNA, and it significantly correlated with ALT (P < 0.0001) and AST (P < 0.0001) during full-blown rejection. In conclusion, we established the Gcf-DNA size profile in patients who have undergone living-related LTx and established a potential biomarker to monitor graft function after LTx.
基金：
Capital Special Program for Health Research and Development; Beijing Municipal Administration of Hospitals Ascent Plan [DFL20150101]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区生物
小类|3 区内分泌学与代谢3 区遗传学3 区医学：研究与实验
最新[2025]版：
大类|2 区生物学
小类|2 区遗传学2 区医学：研究与实验3 区内分泌学与代谢
JCR分区：
出版当年[2017]版：
Q2ENDOCRINOLOGY & METABOLISMQ2MEDICINE, RESEARCH & EXPERIMENTALQ2GENETICS & HEREDITY
最新[2023]版：
Q2ENDOCRINOLOGY & METABOLISMQ2GENETICS & HEREDITYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[a]Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
共同第一作者：
通讯作者：
通讯机构：[a]Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China[b]Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China[g]The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics, Hong Kong SAR, China[*1]Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China.[*2]Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
推荐引用方式(GB/T 7714)：
Hoi Ioi Ng,Xiaofan Zhu,Liming Xuan,et al.Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism[J].MOLECULAR GENETICS and METABOLISM.2019,127(1):45-50.doi:10.1016/j.ymgme.2019.03.004.
APA：
Hoi Ioi Ng,Xiaofan Zhu,Liming Xuan,Yan Long,Yan Mao...&Zhijun Zhu.(2019).Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism.MOLECULAR GENETICS and METABOLISM,127,(1)
MLA：
Hoi Ioi Ng,et al."Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism".MOLECULAR GENETICS and METABOLISM 127..1(2019):45-50
