通过液体活检检测无症状HBsAg血清反应阳性患者的早期肝细胞

StephenW

Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy
Chunfeng Qu, Yuting Wang, Pei Wang, Kun Chen, Minjie Wang, Hongmei Zeng, Jianquan Lu, Qianqian Song, Bill H. Diplas, Da Tan, Chunsun Fan, Qigao Guo, Zheng Zhu, Huihui Yin, Liping Jiang, Xixi Chen, Hui Zhao, Huan He, Yong Wang, Guangyu Li, Xinyu Bi, Xinming Zhao, Taoyang Chen, Hongping Tang, Chuanguo Lv, Dongmei Wang, Wanqing Chen, Jianguo Zhou, Hong Zhao, Jianqiang Cai, Xiaoyue Wang, Sizhen Wang, Hai Yan , Yi-Xin Zeng, Webster K. Cavenee, and Yuchen Jiao
PNAS March 26, 2019 116 (13) 6308-6312; published ahead of print March 11, 2019 https://doi.org/10.1073/pnas.1819799116
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    Contributed by Webster K. Cavenee, January 25, 2019 (sent for review November 20, 2018; reviewed by Zhenghe Wang and Jian Yu)

  
Significance

</ br> </ br> </ br> High sensitivity in the detection of cfDNA mutations. The assay successfully identified four early-stage HCC cases (<3 cm) from 331 HBsAg (+) individuals who were negative based on screening with serum AFP and ultrasonography. The positive predictive value was 17% , which was much higher than in previous studies. This paper shows that the combination of cfDNA and serum protein markers has significant promise for the early detection of HCC in the community population.
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 The developed cohort consist of of individuals who have 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 case s 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 were 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.

        Cell free DNA hepatocellular carcinoma early detection of cancer HBsAg-seropositive

StephenW

通过液体活检检测无症状HBsAg血清反应阳性患者的早期肝细胞癌
曲春峰，王玉婷，王培，陈坤，王敏杰，曾红梅，卢建全，宋倩倩，比尔H. Diplas，大谭，范春荪，郭启高，郑竺，尹慧慧，江丽萍，陈西熙，赵辉，何欢，王勇，李光宇，毕新宇，赵新明，陈桃阳，唐红平，吕传国，王冬梅，陈万庆，周建国，赵红，蔡建强，王晓月，王思珍，海燕，曾益新，Webster K. Cavenee和Yuchen Jiao
PNAS 2019年3月26日116（13）6308-6312;发布于2019年3月11日之前的出版物https://doi.org/10.1073/pnas.1819799116
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供稿人：Webster K. Cavenee，2019年1月25日（发送于2018年11月20日审查;由Zhenghe Wang和Jian Yu审阅）


意义

</ br> </ br> </ br>检测cfDNA突变的灵敏度很高。该试验成功鉴定了来自331名HBsAg（+）个体的4例早期HCC病例（<3 cm），这些病例均为血清AFP和超声检查阴性。阳性预测值为17％，远高于之前的研究。本文表明，cfDNA和血清蛋白标记物的结合对于社区人群中HCC的早期检测具有重要意义。
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作为病例，健康个体作为对照。开发的队列由具有肝结节和/或血清甲胎蛋白（AFP）水平升高的个体组成，并且测试结果强有力。将患有HCC的患者与非HCC患者分开，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）。我们的研究提供的证据表明，使用cfDNA改变和蛋白质标记物的联合检测是鉴定具有未知HCC状态的无症状社区人群的早期HCC的可行方法。

无细胞DNA肝细胞癌早期检测癌症HBsAg血清阳性