Circulating DNA methylation profile improves the accuracy of serum biomarkers for the detection of nonmetastatic hepatocellular carcinoma.

This study exploited hepatocellular carcinoma (HCC)-specific circulating DNA methylation profiles to improve the accuracy of a current screening assay for HCC patients in high-risk populations. Differentially methylated regions in cell-free DNA between 58 nonmetastatic HCC and 121 high-risk patients with liver cirrhosis or chronic hepatitis were identified and used to train machine learning classifiers. The model could distinguish HCC from high-risk non-HCC patients in a validation cohort, with an area under the curve of 0.84. Combining these markers with the three serum biomarkers (AFP, lectin-reactive AFP, des-γ-carboxy prothrombin) in a commercial test, μTASWako, achieved an area under the curve of 0.87 and sensitivity of 68.8% at 95.8% specificity. HCC-specific circulating DNA methylation markers may be added to the available assay to improve the early detection of HCC.