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

Abstract

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