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

被引：9

作者：

Phan, Thanh Hai ^{[1
]}

Nguyen, Van Thien Chi ^{[2
,3
]}

Pham, Thu Thuy Thi ^{[1
]}

Nguyen, Van-Chu ^{[4
,5
]}

Ho, Tan Dat ^{[1
]}

Pham, Thi Mong Quynh ^{[2
,3
]}

Thanh-Huong, Tran ^{[4
,5
]}

Nguyen, Thanh Dat ^{[2
,3
]}

Khang Le, Nguyen Duy ^{[2
,3
]}

Nguyen, Trong-Hieu ^{[2
,3
]}

Duong, Minh-Long ^{[4
]}

Bach, Hoai-Phuong Thi ^{[4
]}

Kim, Van-Vu ^{[4
,5
]}

Pham, The-Anh ^{[4
]}

Nguyen, Bao Toan ^{[1
]}

Vo Nguyen, Thanh Nhan ^{[1
]}

Nguyen, Thanh Dang ^{[1
]}

Bieu Phu, Dung Thai ^{[1
]}

Huu Phan, Boi Hoan ^{[1
]}

Nguyen, Duy-Sinh ^{[6
]}

Truong, Dinh-Kiet ^{[2
]}

Do, Thanh-Thuy Thi ^{[2
]}

Giang, Hoa ^{[2
,3
]}

Nguyen, Hoai-Nghia ^{[2
,3
]}

Phan, Minh-Duy ^{[2
,3
]}

Tran, Le Son ^{[2
,3
]}

机构：

[1] Med Med Ctr, Ho Chi Minh City, Vietnam

[2] Med Genet Inst, Ho Chi Minh City, Vietnam

[3] Gene Solut, Ho Chi Minh City, Vietnam

[4] Natl Canc Hosp, Hanoi, Vietnam

[5] Hanoi Med Univ, Hanoi, Vietnam

[6] Nguyen Tat Thanh Univ, Fac Med, Dept Oncol, Ho Chi Minh City, Vietnam

来源：

FUTURE ONCOLOGY | 2022年 / 18卷 / 39期

关键词：

cell-free DNA; circulating tumor DNA; DNA methylation; early detection; GALAD; hepatocellular carcinoma; machine learning; mu TASWako; DES-GAMMA CARBOXYPROTHROMBIN; ALPHA-FETOPROTEIN; EARLY-DIAGNOSIS; PLASMA DNA; MARKER; CANCER; TUMOR; SURVEILLANCE; PATHOGENESIS; PROTHROMBIN;

D O I：

10.2217/fon-2022-1218

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-gamma-carboxy prothrombin) in a commercial test, mu TASWako (R), 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. The early detection of liver cancer in high-risk populations can help people with the disease have a higher chance of survival and better quality of life. However, this is still a healthcare challenge. Current commercial blood tests measuring protein signatures in the blood have low accuracy due to increased levels of these proteins being detected in both liver cancer patients and patients with chronic liver diseases. In this study, we identified a set of signatures in DNA released by cancer cells into the bloodstream and used them as biomarkers to distinguish liver cancer patients from high-risk patients. We also demonstrated that adding those signatures to a commercial blood test currently used in clinics could improve the accuracy in detecting liver cancer patients.

引用

页码：4399 / 4413

页数：15