5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer

作     者：Ji Zhang Xiao Han Chunchun Gao Yurong Xing Zheng Qi Ruijuan Liu Yueqin Wang Xiaojian Zhang Yun-Gui Yang Xiangnan Li Baofa Sun Xin Tian 

作者机构：Department of Pharmacy The First Affiliated Hospital of Zhengzhou University Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou University Sino-Danish College University of Chinese Academy of Sciences Physical Examination Center The First Affiliated Hospital of Zhengzhou University Department of Anesthesiology The First Affiliated Hospital of Zhengzhou University CAS Key Laboratory of Genomic and Precision Medicine School of Future Technology Beijing Institute of GenomicsChinese Academy of Sciences Institute of Stem Cell and Regeneration Chinese Academy of Sciences Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou University 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2018年第16卷第3期

页      面：187-199页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the Ministry of Science and Technology of China (Grant No. 2016YFC0900300) National Natural Science Foundation of China (Grant Nos. 31670895, U1504831, 31430022, 31670824, 31400672, and 81703598) Major Science and Technology Project of Henan Province (Grant No. 161100310100) Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB14030300) Foundation for University Young Key Teacher of Henan Province (Grant No. 2015GGJS-162) Science and Technology Project of Henan Province (Grant No.162102310199), China 

主　　题：5-Hydroxymethylcytosine Lung cancer Cell-free DNA Biomarker 5hmC-Seal 

摘      要：Non-small-cell lung cancer （NSCLC）, the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymetbylcytosine （ShmC） signatures in circulating cell-free DNA （cfDNA） that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminat- ing tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identi- fied six potential biomarkers from 66 patients and 67 healthy controls （mean decrease accuracy 〉 3.2, P 〈 3.68E-19） using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient＇s cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.