Background: Epigenetic changes, including DNA methylation, are recognized as one of the potential mechanisms involved in the pathogenesis of hepatocellular carcinoma (HCC). Aims: 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. Methods: 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. Results: 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. Conclusions: Our study highlights the role of promoter hypermethylation in the multistep process of hepatocarcinogenesis, providing potential clinical applications in diagnosis and prognosis.
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