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

Author:

Phan Thanh Hai1,Chi Nguyen Van Thien23,Thi Pham Thu Thuy1,Nguyen Van-Chu45,Ho Tan Dat1,Quynh Pham Thi Mong23,Tran Thanh-Huong45,Nguyen Thanh Dat23,Khang Le Nguyen Duy23,Nguyen Trong-Hieu23,Duong Minh-Long4,Bach Hoai-Phuong Thi4,Kim Van-Vu45,Pham The-Anh4,Nguyen Bao Toan1,Vo Nguyen Thanh Nhan1,Nguyen Thanh Dang1,Bieu Phu Dung Thai1,Huu Phan Boi Hoan1,Nguyen Duy-Sinh6,Truong Dinh-Kiet2,Do Thanh-Thuy Thi2,Giang Hoa23,Nguyen Hoai-Nghia23,Phan Minh-Duy23,Tran Le Son23ORCID

Affiliation:

1. MEDIC Medical Center, Ho Chi Minh City, Vietnam

2. Medical Genetics Institute, Ho Chi Minh City, Vietnam

3. Gene Solutions, Ho Chi Minh City, Vietnam

4. National Cancer Hospital, Hanoi, Vietnam

5. Hanoi Medical University, Hanoi, Vietnam

6. Department of Oncology, Faculty of Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam

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.

Funder

Gene Solutions

Publisher

Future Medicine Ltd

Subject

Cancer Research,Oncology,General Medicine

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