中国科学家为乙型肝炎携带者开发肝癌的早期诊断

StephenW

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.

StephenW

中国科学家为乙型肝炎携带者开发肝癌的早期诊断
来源：新华社| 2019-03-12 19:33:25 |编辑：ZX

新华社北京3月12日电中国科学家设计了一种新的乙肝携带者筛查方法，用于检测早期肝细胞癌（HCC），这是最常见的原发性肝癌。

这种新方法是由中国医学科学院肿瘤医院和生物医药公司Genetron Health的研究人员开发的。通过液体活检，检测无细胞DNA体细胞突变与蛋白质标记物的结合，研究人员可以有效地识别小于3厘米的早期HCC病例。

根据其中一位研究人员Yan Hai的说法，该方法在验证队列中显示出100％的敏感性，94％的特异性和17％的阳性预测值，证明它是鉴别早期HCC的可行方法。

Yan说，研究小组将通过一项多中心，大型前瞻性队列研究的系统研究来优化这种筛查方法。

经过严格的临床验证，该方法有望成为肝癌的一种更方便，非侵入性和标准化的早期筛查方案。

该研究发表在美国“美国国家科学院院刊”上。

StephenW

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

PMID:
    30858324
DOI:
    10.1073/pnas.1819799116

StephenW

Proc Natl Acad Sci U S A. 2019 Mar 11. pii：201819799.doi：10.1073 / pnas.1819799116。 [印刷前的电子版]
通过液体活检检测无症状HBsAg血清阳性个体的早期肝细胞癌。
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。
作者信息

1
    中国医学科学院北京协和医学院国家癌症中心/国家癌症/肿瘤医院临床研究中心分子肿瘤学国家重点实验室，北京100021; [email protected] [email protected] [email protected]。
2
    中国医学科学院北京协和医学院国家癌症中心/国家肿瘤/肿瘤医院临床研究中心免疫科，100021北京
3
    中国医学科学院北京协和医学院国家癌症中心/国家癌症/肿瘤医院临床研究中心分子肿瘤学国家重点实验室，北京100021
4
    中国医学科学院北京协和医学院国家癌症中心/国家肿瘤/肿瘤医院临床研究中心临床实验室，北京100021
五
    国家癌症登记处，国家癌症中心/中国医学科学院北京协和医学院肿瘤/肿瘤医院国家临床研究中心，北京100021，中国。
6
    启东市肝癌研究所/启东市人民医院，江苏省启东市，226200
7
    杜克大学医学中心杜克大学普雷斯顿罗伯特蒂施脑肿瘤中心，北卡罗来纳州达勒姆27710。
8
    极冷致健康（北京）有限公司，102206北京，中国。
9
    灵璧市疾病预防控制中心，安徽省234200
10
    中国医学科学院北京协和医学院国家癌症中心/国家肿瘤/肿瘤医院临床研究中心诊断放射科，北京100021
11
    中国医学科学院北京协和医学院肿瘤/肿瘤医院国家癌症中心/国家临床研究中心超声检查科，100021北京
12
    中国医学科学院基础医学研究所生物化学与生物信息学中心医学分子生物学国家重点实验室，北京协和医学院基础医学院，北京100005
13
    中国医学科学院北京协和医学院国家癌症中心/国家肿瘤/肿瘤医院临床研究中心肝胆外科，北京100021
14
    中国医学科学院北京协和医学院国家癌症中心/国家癌症/肿瘤医院临床研究中心癌症筛查办公室，北京100021，中国。
15
    中山大学肿瘤防治中心实验研究室，华南国家重点实验室，肿瘤医学协同创新中心，广州。
16
    路德维希癌症研究所，加利福尼亚大学圣地亚哥分校，加利福尼亚州拉霍亚，92093-0660，quchf @ cicams.ac.cn，电子邮件：[email protected]，jiaoyuchen，126.com。

抽象

基于无细胞DNA（cfDNA）和蛋白质的液体活检显示了检测不同组织类型的早期癌症的潜力。然而，大多数这些研究是回顾性的，使用先前被诊断患有癌症的个体和作为对照的健康个体。在这里，我们开发了一种液体活检检测，命名为肝细胞癌筛查（HCCscreen），以从社区人群中乙型肝炎病毒（HBsAg）阳性无症状个体的表面抗原中鉴定HCC。训练组由具有肝结节和/或升高的血清甲胎蛋白（AFP）水平的个体组成，并且该测定法将HCC患者与非HCC患者分离，敏感性为85％，特异性为93％。 。我们进一步将该测定应用于具有正常肝脏超声和血清AFP水平的331个个体。共鉴定出24例阳性病例，临床随访6-8个月确诊4例发生HCC。在相同的时间表中，在随访中没有从307个测试阴性个体中诊断出HCC病例。因此，该测定在验证群组中显示100％灵敏度，94％特异性和17％阳性预测值。值得注意的是，四个HCC病例中的每一个在诊断时都处于早期阶段（<3 cm）。我们的研究提供了使用cfDNA改变和p的联合检测的证据

9病成医