Circulating DNA Methylation Profile Improves the Accuracy of Serum Biomarkers for the Detection Of Nonmetastatic Hepatocellular Carcinoma
Thanh Hai Phan, Van Thien Chi Nguyen, Thu Thuy Thi Pham, Chu Van Nguyen, Tan Dat Ho, Thi Mong Quynh Pham, Thanh-Huong Tran, Thanh Dat Nguyen, Nguyen Duy Khang Le, Trong-Hieu Nguyen, Minh-Long Duong, Hoai-Phuong Thi Bach, Van-Vu Kim, The-Anh Pham, Bao Toan Nguyen, Thanh Nhan Vo Nguyen, Thanh Dang Nguyen, Dung Thai Bieu Phu, Boi Hoan Huu Phan, Duy-Sinh Nguyen, Dinh‐Kiet Truong, Thanh‐Thuy Thi, Hoa Giang, Hoai‐Nghia Nguyen, Minh‐Duy Phan, Le Son Tran
Abstract
Aim: 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. Methods: 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. Results: 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. Conclusion: HCC-specific circulating DNA methylation markers may be added to the available assay to improve the early detection of HCC.