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;
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.
Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6308-6312. doi: 10.1073/pnas.1819799116. Epub 2019 Mar 11.
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.
液体活检基于游离 DNA（cfDNA）和蛋白质，已显示出检测多种组织类型早期癌症的潜力。然而，这些研究大多是回顾性的，将先前被诊断患有癌症的个体作为病例，将健康个体作为对照。在这里，我们开发了一种液体活检检测方法，命名为肝细胞癌筛查（HCCscreen），用于从社区人群中乙型肝炎表面抗原（HBsAg）阳性的无症状个体中识别 HCC。训练队列由有肝结节和/或血清α-胎蛋白（AFP）水平升高的个体组成，该检测方法能够灵敏地将 HCC 患者与非 HCC 患者区分开来，其灵敏度为 85%，特异性为 93%。我们进一步将该检测方法应用于 331 名肝脏超声和血清 AFP 水平正常的个体。共发现 24 例阳性病例，临床随访 6-8 个月证实其中 4 例发展为 HCC。在相同时间范围内，对 307 例随访检测阴性的个体中未诊断出 HCC 病例。因此，该检测方法在验证队列中显示出 100%的灵敏度、94%的特异性和 17%的阳性预测值。值得注意的是，诊断时这 4 例 HCC 病例均处于早期（<3cm）阶段。我们的研究提供了证据，表明联合检测 cfDNA 改变和蛋白质标志物是一种从具有未知 HCC 状态的无症状社区人群中识别早期 HCC 的可行方法。
