State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Moores Cancer Center and Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Nat Mater. 2017 Nov;16(11):1155-1161. doi: 10.1038/nmat4997. Epub 2017 Oct 9.
An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.
尚未开发出一种有效的用于肝细胞癌 (HCC) 诊断和预后的基于血液的方法。携带癌症特异性遗传和表观遗传异常的循环肿瘤 DNA (ctDNA) 可能能够进行非侵入性的“液体活检”以用于癌症的诊断和监测。在这里，我们通过比较 HCC 组织和正常血液白细胞，确定了一个 HCC 特异性甲基化标记物panel，并表明 HCC 肿瘤 DNA 和匹配的血浆 ctDNA 的甲基化谱高度相关。使用来自 1098 例 HCC 患者和 835 例正常对照的 cfDNA 样本，我们构建了一个诊断预测模型，该模型显示出高诊断特异性和敏感性（P < 0.001），并且与肿瘤负担、治疗反应和分期高度相关。此外，我们构建了一个预后预测模型，该模型有效地预测了预后和生存（P < 0.001）。总的来说，这些发现证明了 ctDNA 甲基化标记物在 HCC 的诊断、监测和预后中的实用性。
