Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for early diagnosis and follow up after treatment is one of the clinical obstacles for effective treatment of HCC. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still lacking of evidence of its clinical use. The aim of this study is to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation (APC-MET) as a potential biomarker in HCC treatment. Method: A total of 96 patients with HCC at BCLC stage B underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined from the plasma of each patients before and 1 months after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment were analyzed, and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using cox regression analysis. Results: Univariate cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI 1.05－8.05, p=0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI 1.16－10.4, p=0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI 1.21－3.44, p=0.007). In multivariate models, pre-op APC-MET >0 was a significant predictor of disease progression after adjusting with other two traditional biomarkers (HR, 1.82, 95% CI 1.05－3.17, p=0.034). Conclusions: Hypermethylation of APC promoter appears to be a potential new biomarker that could predict patient survival and disease progression outcome in patients with intermediate stage HCC after local ablation treatment.