International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Eastern Hepatobiliary Surgery Institute/hospital, Shanghai, 200438, People's Republic of China.
Department of Radiotherapy Oncology, General Hospital of Northern Theater Command, Shenyang, 110016, People's Republic of China.
J Hematol Oncol. 2023 Jan 5;16(1):1. doi: 10.1186/s13045-022-01396-z.
Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising.
Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes.
An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.
肝细胞癌（HCC）通常起源于肝硬化（LC）背景。建议对患有肝硬化和疑似 HCC 的患者进行血清生物标志物检测和影像学诊断评估。然而，常规诊断方法在检测早期 HCC 方面的性能仍不理想。
本研究在中国九个省份的九个临床中心，对 1675 名参与者（包括 490 名健康对照者、577 名 LC 患者和 608 名 HCC 患者）进行了一项大规模、多中心研究，采用 Circulating Single-Molecule Amplification and Resequencing Technology（cSMART），通过检测 21 个基因中的 931 个突变位点，对游离 DNA（cfDNA）的基因突变特征进行了分析。
通过联合三个突变位点和三个血清生物标志物，建立了一种名为“联合方法”的综合诊断模型。与 AFP 相比，联合方法在 HCC 的诊断中表现更好，尤其是早期 HCC，其各阶段的敏感性分别为 81.25%和 66.67%。重要的是，该综合模型在区分 AFP 阴性、AFP-L3 阴性和 PIVKA-II 阴性 HCC 与 LC 方面具有很高的准确性。
