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

Oncology. 2024;102(11):935-943. doi: 10.1159/000538455. Epub 2024 Mar 25.

Abstract

Introduction: 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.

Method: 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.

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, preoperative APC-MET >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, p = 0.034).

Conclusions: 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.

Keywords: Biomarker; DNA methylation; Hepatocellular carcinoma; Local ablation; Outcome.

MeSH terms

  • Adenomatous Polyposis Coli Protein* / genetics
  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / surgery
  • DNA Methylation*
  • Female
  • Humans
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • Adenomatous Polyposis Coli Protein