Preoperative serum methylation signature as prognostic tool after curative hepatectomy in patients with hepatocellular carcinoma

Anticancer Res. 2015 Feb;35(2):997-1007.

Abstract

Aim: This study aimed to investigate the relationship between prognosis after curative hepatectomy and serum methylation signature (SMS), defined by methylation levels of six specific genes (cyclin D2, Ras association (RalGDS/AF-6) domain family member 1, serine peptidase inhibitor Kunitz type 2, cystic fibrosis transmembrane conductance regulator, brain abundant membrane attached signal protein 1, and steroid-5-alpha-reductase alpha polypeptide 2).

Patients and methods: Serum samples were collected preoperatively from 125 patients with hepatocellular carcinoma associated with hepatitis C virus infection who underwent curative hepatectomy. We measured the methylation levels of the preceding six genes. We defined the methylation of three genes or more in the serum as SMS-positive in this study. We investigated the prognosis of SMS-positive patients.

Results: SMS-positive patients exhibited significantly shorter disease-free survival (DFS) and overall survival (OS) than SMS-negative patients (p=0.0002 and p<0.0001, respectively). Multivariate analysis showed that SMS positivity was an independent risk factor for shorter DFS (hazard ratio (HR)=2.182; p<0.001) and OS (HR=4.198; p<0.001).

Conclusion: SMS is useful as a prognostic predictor in patients with hepatocellular carcinoma after curative hepatectomy.

Keywords: HCC; cell-free DNA; epigenetic; methylation; quantitative MSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery*
  • Hepatectomy*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery*
  • Methylation
  • Prognosis