title: Serum miRNAs as predictive and preventive biomarker for pre-clinical hepatocellular carcinoma.
abstract: The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6-12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using α-fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations.
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China.
authors: Liang
authors: L
authors: Li
authors: Qidong Liver Cancer Institute and Nantong University Liver Cancer Institute, QiDong 226200, Jiangsu, China.
authors: Jianguo
authors: J
authors: Chen
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China.
authors: Xin
authors: X
authors: Chen
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China.
authors: Jing
authors: J
authors: Tang
authors: MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan 430030, China.
authors: Huan
authors: H
authors: Guo
authors: State Key Lab of Genetic Engineering and MOE Key Lab of Contemporary Anthropology, TaiZhou Institute of Health Sciences and School of Life Sciences, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors: Xiaofeng
authors: X
authors: Wang
authors: State Key Lab of Genetic Engineering and MOE Key Lab of Contemporary Anthropology, TaiZhou Institute of Health Sciences and School of Life Sciences, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors: Ji
authors: J
authors: Qian
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China.
authors: Guijuan
authors: G
authors: Luo
authors: State Key Lab Breeding Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China.
authors: Fangping
authors: F
authors: He
authors: State Key Lab Breeding Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China.
authors: Xiaomei
authors: X
authors: Lu
authors: Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors: Yibo
authors: Y
authors: Ding
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Yingchen
authors: Y
authors: Yang
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Wentao
authors: W
authors: Huang
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Guojun
authors: G
authors: Hou
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Ximeng
authors: X
authors: Lin
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Qin
authors: Q
authors: Ouyang
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Hengyu
authors: H
authors: Li
authors: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors: Ruoyu
authors: R
authors: Wang
authors: Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Hospital of Jiangsu Province, Nanjing, China.
authors: Feng
authors: F
authors: Jiang
authors: Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors: Rui
authors: R
authors: Pu
authors: Qidong Liver Cancer Institute and Nantong University Liver Cancer Institute, QiDong 226200, Jiangsu, China.
authors: Jianhua
authors: J
authors: Lu
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China.
authors: Mudan
authors: M
authors: Jin
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China.
authors: Yexiong
authors: Y
authors: Tan
authors: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Frank J
authors: FJ
authors: Gonzalez
authors: Department of Epidemiology, Second Military Medical University, Shanghai 200433, China.
authors: Guangwen
authors: G
authors: Cao
authors: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors: Mengchao
authors: M
authors: Wu
authors: State Key Lab Breeding Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China.
authors: Hao
authors: H
authors: Wen
authors: MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan 430030, China.
authors: Tangchun
authors: T
authors: Wu
authors: State Key Lab of Genetic Engineering and MOE Key Lab of Contemporary Anthropology, TaiZhou Institute of Health Sciences and School of Life Sciences, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors: Li
authors: L
authors: Jin
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China; Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: Chenlei@smmu.edu.cn.
authors: Lei
authors: L
authors: Chen
authors: International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai, China; National Laboratory for Oncogenes and Related Genes, Cancer Institute, RenJi Hospital, Shanghai Jiao Tong University, Shanghai 200441, China. Electronic address: hywangk@vip.sina.com.
authors: Hongyang
authors: H
authors: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D035683:MicroRNAs / Q000097:blood*; D012372:ROC Curve; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D000509:alpha-Fetoproteins
keywords: Biomarker; Circulating miRNAs; Hepatocellular carcinoma; Prediction; Prevention