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

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.