Author:
Wu Tong,Fan Rong,Bai Jian,Yang Zhao,Qian Yun-Song,Du Lu-Tao,Wang Chun-Ying,Wang Ying-Chao,Jiang Guo-Qing,Zheng Dan,Fan Xiao-Tang,Zheng Bo,Liu Jing-Feng,Deng Guo-Hong,Shen Feng,Hu He-Ping,Ye Yi-Nong,Zhang Qing-Zheng,Zhang Jing,Gao Yan-Hang,Xia Jie,Yan Hua-Dong,Liang Min-Feng,Yu Yan-Long,Sun Fu-Ming,Gao Yu-Jing,Sun Jian,Zhong Chun-Xiu,Wang Yin,Wang Hui,Kong Fei,Chen Jin-Ming,Wen Hao,Wu Bo-Ming,Wang Chuan-Xin,Wu Lin,Hou Jin-Lin,Liu Xiao-Long,Wang Hong-Yang,Chen Lei
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Funder
National Natural Science Foundation of China
Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program
Sanming Project of Medicine in Shenzhen
National Science Foundation of Shanghai
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology