Chinese scientists develop early diagnosis of liver cancer for hepatitis B carriers
Source: Xinhua| 2019-03-12 19:33:25|Editor: ZX
BEIJING, March 12 (Xinhua) -- Chinese scientists have designed a new screening method for hepatitis B carriers, to detect early-stage hepatocellular carcinoma (HCC), the most common type of primary liver cancer.
The new method was developed by researchers from Cancer Hospital, Chinese Academy of Medical Sciences and Genetron Health, a biomedical company. Through a liquid biopsy that detects cell-free DNA somatic mutations in combination with protein markers, researchers can efficiently identify early-stage HCC cases of less than 3 cm.
According to Yan Hai, one of the researchers, the method showed 100 percent sensitivity, 94 percent specificity and 17 percent positive predictive value in the validation cohort, proving it a feasible approach to identify early stage HCC.
The research team will optimize this screening method through systematic research in a multi-center, large prospective cohort study, Yan said.
After rigorous clinical validation, this method is expected to become a more convenient, non-invasive and standardized early screening program for liver cancer.
The research was published in the U.S. journal Proceedings of the National Academy of Sciences. 作者: StephenW 时间: 2019-3-13 14:00
Proc Natl Acad Sci U S A. 2019 Mar 11. pii: 201819799. doi: 10.1073/pnas.1819799116. [Epub ahead of print]
Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.
Qu C1,2, Wang Y3,2, Wang P3, Chen K3,2, Wang M4, Zeng H5, Lu J6, Song Q3, Diplas BH7, Tan D8, Fan C6, Guo Q9, Zhu Z10, Yin H3, Jiang L8, Chen X8, Zhao H9, He H3,2, Wang Y11, Li G12, Bi X13, Zhao X10, Chen T6, Tang H6, Lv C6, Wang D3,2, Chen W14, Zhou J13, Zhao H13, Cai J13, Wang X12, Wang S8, Yan H7, Zeng YX15, Cavenee WK16, Jiao Y1.
Author information
1
State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China; [email protected][email protected][email protected].
2
Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
3
State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
4
Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
5
National Cancer Registration Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, P. R. China.
6
Qidong Liver Cancer Institute/Qidong People's Hospital, Qidong, 226200 Jiangsu Province, China.
7
The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710.
8
Genetron Health (Beijing) Co. Ltd., 102206 Beijing, China.
9
Lingbi Center for Disease Control and Prevention, 234200 Anhui Province, China.
10
Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
11
Department of Ultrasonography, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
12
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
13
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, China.
14
Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 Beijing, P. R. China.
15
Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
16
Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093-0660 [email protected][email protected][email protected].
Abstract
Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
KEYWORDS:
HBsAg-seropositive; cell free DNA; early detection of cancer; hepatocellular carcinoma
