• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Gut: Journal of the British Society of Gastroenterology >Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma
【24h】

Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma

机译：在循环无细胞DNA中的5-羟甲基胞嘧啶的基因组映射作为早期检测肝细胞癌的非侵入性方法

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC.Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection.The 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95%?CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0?cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95%?CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history).We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
机译：缺乏高度敏感和特定的诊断生物标志物是对肝细胞癌患者（HCC）患者差的主要原因。我们试图使用循环无细胞DNA（CFDNA）进行非侵入性诊断方法，用于早期检测HCC。施加5HMC-密封技术，我们在2554例中获得了CFDNA样品中的基因组5-羟甲基胞嘧啶（5HMC）主题：1204例HCC患者，392例慢性乙型肝炎病毒感染（CHB）或肝硬化（LC）和958名健康个体和良性肝病变患者。通过使用弹性净规范化进行特征选择的案例控制分析开发了早期HCC的诊断模型。来自HCC患者的5HMC密封数据显示了富含肝脏衍生的增强剂标记的基因组分布。我们开发了一种32-基因诊断模型，可根据非HCC（验证集：曲线下面积（AUC）= 88.4％的面积（AUC）= 88.4％;（95％？ CI 85.8％至91.1％）），表现出优异的α-胎蛋白（AFP）的性能。除了从非HCC患有早期或小肿瘤（例如，≤2.0℃）的患者外，5HMC模型显示出与CHB或LC历史的高风险受试者区分早期HCC的高容量（验证集：AUC = 84.6％; （95％？CI 80.6％至88.7％）），也显着优于AFP。此外，5HMC诊断模型似乎独立于潜在的混乱（例如，吸烟/酒精摄入历史）。我们已经开发并验证了具有临床应用潜力的非侵入性方法，以便早期检测HCC仍然在高处风险个人。

著录项

  • 来源
  • 作者

    Jiabin Cai; Lei Chen; Zhou Zhang; Xinyu Zhang; Xingyu Lu; Weiwei Liu; Guoming Shi; Yang Ge; Pingting Gao; Yuan Yang; Aiwu Ke; Linlin Xiao; Ruizhao Dong; Yanjing Zhu; Xuan Yang; Jiefei Wang; Tongyu Zhu; Deping Yang; Xiaowu Huang; Chengjun Sui; Shuangjian Qiu; Feng Shen; Huichuan Sun; Weiping Zhou; Jian Zhou; Ji Nie; Chang Zeng; Emily Kunce Stroup; Xu Zhang; Brian C-H Chiu; Wan Yee Lau; Chuan He; Hongyang Wang; Wei Zhang; Jia Fan;

  • 作者单位

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    The International Cooperation Laboratory on Signal Transduction The Eastern Hepatobiliary Surgery;

    Department of Preventive Medicine Northwestern University Feinberg School of Medicine;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Shanghai Epican Genetech Co. Ltd;

    Department of Laboratory Medicine The Tenth People’s Hospital of Shanghai Tongji University;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    School of Public Health Shanghai Jiao Tong University School of Medicine;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Hepatobiliary Surgery The Eastern Hepatobiliary Surgery Hospital The Second Military;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Laboratory Medicine Shanghai Jiao Tong University;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    The International Cooperation Laboratory on Signal Transduction The Eastern Hepatobiliary Surgery;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Shanghai Public Health Clinic Center Fudan University;

    Shanghai Public Health Clinic Center Fudan University;

    Department of Laboratory Medicine Zhoupu Hospital Shanghai University of MedicineandHealth Sciences;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Hepatobiliary Surgery The Eastern Hepatobiliary Surgery Hospital The Second Military;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Hepatobiliary Surgery The Eastern Hepatobiliary Surgery Hospital The Second Military;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Hepatobiliary Surgery The Eastern Hepatobiliary Surgery Hospital The Second Military;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

    Department of Chemistry University of Chicago;

    Department of Preventive Medicine Northwestern University Feinberg School of Medicine;

    Driskill Graduate Program in Life Sciences Northwestern University Feinberg School of Medicine;

    Department of Medicine University of Illinois;

    Department of Public Health Sciences University of Chicago;

    Faculty of Medicine The Chinese University of Hong Kong New Territories;

    Department of Chemistry University of Chicago;

    The International Cooperation Laboratory on Signal Transduction The Eastern Hepatobiliary Surgery;

    Department of Preventive Medicine Northwestern University Feinberg School of Medicine;

    Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
  • 关键词

    hepatobiliary cancer; hepatocellular carcinoma; cancer;

    机译：肝胆癌;肝细胞癌;癌症;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号