Abstract
BACKGROUND: Primary liver cancer (PLC) is a global health concern. The plasma dual-target methylation (PDTM) test, which interrogates the methylation status of GNB4 and Riplet, exhibits a commendable ability to discriminate hepatocellular carcinoma (HCC) from controls. Nevertheless, its performance in detecting PLC in larger populations remains to be validated. RESULTS: A multicenter, double-blind, cross-sectional study was conducted. Blood samples were collected from all participants for the PDTM test, which is based on a triplex quantitative methylation-specific polymerase chain reaction (qMSP) platform. Additionally, Sanger sequencing was performed to confirm the accuracy of methylation detection by the PDTM test. The study enrolled 430 PLC patients and 752 controls. The PDTM test demonstrated an overall sensitivity of 92.3% (95% confidence interval [CI], 89.4-94.7) for PLC patients and an overall specificity of 93.4% (95% CI, 91.3-95.0) for controls with benign liver disease (BLD) or non-liver primary malignancies (NLPM). Specifically, the sensitivities of the PDTM test for patients with HCC, intrahepatic cholangiocarcinoma (ICC) or early-stage (TNM stages I and II) PLC were 91.9% (95% CI, 87.6-95.0), 93.3% (95% CI, 85.9-97.5) and 88.7% (95% CI, 83.9-92.5), respectively. Furthermore, the kappa values for both GNB4 and Riplet between the PDTM test and Sanger sequencing exceeded 0.99, indicating a high level of consistency. CONCLUSIONS: The PDTM test demonstrates excellent diagnostic performance for PLC, particularly in cases of early-stage PLC. It is a promising early screening or surveillance tool for PLC, and further prospective research is required to ascertain its full utility.