Hepatocellular carcinoma suppressor 1 promoter hypermethylation in serum. A diagnostic and prognostic study in hepatitis B

Clin Res Hepatol Gastroenterol. 2017 Mar;41(2):171-180. doi: 10.1016/j.clinre.2016.10.003. Epub 2017 Feb 8.

Abstract

Background: Liver cancer ranks as the second leading cause of cancer-related mortality in man worldwide, and hepatocellular carcinoma (HCC) is the most prevalent malignant neoplasm of the liver. The sensitivity of alpha-fetoprotein (AFP) as an HCC diagnostic marker for HCC diagnosis is 39-65%, and one-third patients with HCC are missed using AFP. New biomarkers are needed to diagnose HCC at an earlier stage and to individualize treatment strategies. Hepatocellular carcinoma suppressor 1 (HCCS1) is a newly identified liver tumor suppressor gene.

Objective: Our study evaluated the diagnostic value of serum HCCS1 promoter methylation in patients with HCC associated with hepatitis B.

Methods: We determined the methylation status of serum HCCS1 promoter in 120 patients with HCC, 146 patients with chronic hepatitis B (CHB) and 27 healthy controls (HCs) by methylation-specific polymerase chain reaction (MSP). Evaluation of a cohort with 63 patients with HCC and 44 patients with CHB was set as a validation dataset.

Results: The frequency of HCCS1 promoter methylation in patients with HCC was significantly higher than that in patients with CHB (P<0.001) and HCs (P<0.001), and was associated with tumor node-metastasis (TNM) stage (P=0.01). The sensitivity of serum HCCS1 promoter methylation for discriminating patients with HCC from CHB was 62.5% and that of AFP alone was 55%. Notably, the sensitivity of serum HCCS1 promoter methylation plus AFP level was 81.7%.

Conclusion: HCCS1 has potential as a biomarker for diagnosis and prognosis of patients with HCC.

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • DNA / blood*
  • DNA Methylation*
  • Female
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / genetics
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Reproducibility of Results
  • Vesicular Transport Proteins / blood
  • Vesicular Transport Proteins / genetics*
  • alpha-Fetoproteins / analysis

Substances

  • Biomarkers, Tumor
  • VPS53 protein, human
  • Vesicular Transport Proteins
  • alpha-Fetoproteins
  • DNA