Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma

Abstract

Objectives: Circulating cell-free DNA (cfDNA) is a potential biomarker for tumor diagnosis. Hepatocyte damage is a characteristic component of the pathobiology of hepatocellular carcinoma (HCC), which would be expected to result in substantial leakage of cfDNA into the circulation. However, the diagnostic value of cfDNA levels for HCC remains unclear. Methods: Plasma samples were collected from 24 HCC patients and 62 hepatitis B virus-related liver fibrosis patients. Plasma cfDNA levels were quantified by Qubit method. Results: Plasma cfDNA levels were associated with the degree of liver inflammation, body mass index, and alpha-fetoprotein (AFP) level, but were not associated with fibrosis stages. Plasma cfDNA levels were significantly higher in HCC patients than in non-HCC patients. Multivariate analysis revealed that age and cfDNA, rather than AFP, were independent predictors of HCC. The HCC index, a combination model including age, cfDNA, and AFP, had an area of 0.98 (95% confidence interval 0.92–1.00) under the receiver operating characteristics curve for the diagnosis of HCC at the cut-off value of 0.61, with 87.0% sensitivity and 100% specificity. The diagnostic power of the HCC index was superior to that of cfDNA alone and AFP alone. Conclusions: These results suggest that the combination of cfDNA with age and AFP could improve the diagnostic performance for HCC.

Keywords

• Circulating cell-free DNA
• Hepatocellular carcinoma