HKG Epitherapeutics Ltd. Unit 313-315, 3/F Biotech Center 2, 11 Science Park west Avenue, Shatin, Hong Kong, SAR, China.
Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
Nat Commun. 2023 Jun 7;14(1):3306. doi: 10.1038/s41467-023-39055-7.
High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene CpG site effectively differentiates HCC samples from other blood samples, normal tissues, and non-HCC tumors in TCGA and GEO data repositories. The markers were validated in a separate plasma sample dataset from HCC patients and controls. We designed a high-throughput assay using next-generation sequencing and multiplexing techniques, analyzing plasma samples from 554 clinical study participants, including HCC patients, non-HCC cancers, chronic hepatitis B, and healthy controls. HCC detection sensitivity was 84.5% at 95% specificity and 0.94 AUC. Implementing this assay for high-risk individuals could significantly decrease HCC morbidity and mortality.
高通量测试用于早期癌症检测可以彻底改变公共卫生状况，并降低癌症发病率和死亡率。在这里，我们展示了一种用于液体活检中肝细胞癌（HCC）检测的 DNA 甲基化特征，与正常组织和血液特征明显不同。我们使用四个 CpG 位点开发了一个分类器，并在 TCGA HCC 数据中进行了验证。单个 F12 基因 CpG 位点可有效区分 TCGA 和 GEO 数据存储库中的 HCC 样本与其他血液样本、正常组织和非 HCC 肿瘤。该标志物在来自 HCC 患者和对照的单独血浆样本数据集上得到了验证。我们使用下一代测序和多重技术设计了一种高通量检测方法，分析了来自 554 名临床研究参与者的血浆样本，包括 HCC 患者、非 HCC 癌症、慢性乙型肝炎和健康对照。在 95%特异性和 0.94 AUC 时，HCC 的检测灵敏度为 84.5%。为高危人群实施这种检测方法可以显著降低 HCC 的发病率和死亡率。
