Genetic testing and molecular biomarkers

Aberrant methylation of promoter region of SPINT2/HAI-2 gene: an epigenetic mechanism in hepatitis C virus-induced hepatocarcinogenesis.

PMID 26030814


Epigenetic changes, including DNA methylation, are recognized as one of the potential mechanisms involved in the pathogenesis of hepatocellular carcinoma (HCC). We aimed to study the methylation status of the promoter region of Serine peptidase inhibitor/hepatocyte growth factor activator inhibitor type 2 (SPINT2/HAI-2) tumor suppressor gene in hepatitis C virus (HCV)-infected cirrhotic patients with and without HCC. Methyl-specific polymerase (MSP) chain reaction was used to detect CpG methylation of the SPINT2/HAI-2 gene promoter in peripheral blood samples of 30 HCC and 50 HCV cirrhotic cases, along with 50 normal individuals. Aberrant methylation showed a stepwise increase in frequency from 40% in controls to 64% in HCV cirrhotics, and 66.7% in HCC cases with a significant difference among the studied groups (p=0.021). The combined patient groups had an increased risk of aberrant methylation with an odds ratio (OR) of 2.52, a 95% confidence interval (CI) of 1.23-5.14, and a p-value of 0.05 that became more statistically significant after adjusting for age (OR=2.4, 95% CI=1.13-5.26, p-value=0.012), thereby confirming the association between HCV infection and aberrant methylation. Our study highlights the role of promoter hypermethylation in the multistep process of hepatocarcinogenesis, providing potential clinical applications in diagnosis and prognosis.