BCL6B hypermethylation predicts metastasis and poor prognosis in early-stage hepatocellular carcinoma after thermal ablation

Abstract

Aims: The aim of this study was to evaluate the role of BCL6B methylation in the progression of early-stage hepatocellular carcinoma (HCC) after thermal ablation. Settings and Design: This is a retrospective study and written informed consent was obtained from all patients or their legal guardians. Subjects and Methods: Between October 2008 and December 2013, 73 patients with early-stage HCC within the Milan criteria, who received thermal ablation, were recruited. Statistical Analysis Used: Based on methylation-specific polymerase chain reaction, the relationship between BCL6B methylation and patient characteristics and prognosis was analyzed using univariate, multivariate, and Kaplan–Meier analysis. Results: The median follow-up period was 56 (8–110) months. For the BCL6B unmethylated group, the 1-, 3- and 5-year metastasis and overall survival (OS) rates after thermal ablation were 10.0%, 10.0%, and 40.0% and 100%, 100% and 90.0%, respectively. The 1-, 3-, and 5-year metastasis and OS rates of the methylated group were 23.8%, 66.7% and 88.9% and 66.2%, 71.4% and 41.3%, respectively. Levels of absolute count lymphocyte, serum cholinesterase and albumin in the BCL6B unmethylated group were higher than those in the methylated group (P = 0.020, 0.000, and 0.009, respectively). Kaplan–Meier analysis revealed that BCL6B methylation was related to metastasis and poor prognosis (P = 0.001 and 0.018, respectively). Univariate analysis revealed that BCL6B methylation was a risk factor for metastasis and poor prognosis (odds ratio [OR]: 5.663; 95% confidence interval [CI], 1.745–18.375, P = 0.004 and OR: 3.734; 95% CI, 1.151–12.110, P = 0.028, respectively). Multivariate analysis revealed that BCL6B methylation was an independent risk factor for metastasis (OR: 3.736; 95% CI, 1.000–13.963,P = 0.05) and not for prognosis (OR: 2.780; 95% CI, 0.835–9.250,P = 0.096). Conclusions: BCL6B methylation could be a valuable prognostic factor for metastasis and poor prognosis in early-stage HCC after thermal ablation, which is an independent risk factor for metastasis. Our findings provide insights for combining ablation and epigenetic therapy for patients with HCC.