title: Aberrant methylation of promoter region of SPINT2/HAI-2 gene: an epigenetic mechanism in hepatitis C virus-induced hepatocarcinogenesis.
abstract: BACKGROUND
  Epigenetic changes, including DNA methylation, are recognized as one of the potential mechanisms involved in the pathogenesis of hepatocellular carcinoma (HCC).
  
  
  OBJECTIVE
  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.
authors.affiliation: 1 Department of Chemical Pathology, Alexandria University , Alexandria, Egypt .
authors.forename: Ragaa A
authors.initials: RA
authors.lastname: Ramadan
authors.affiliation: 1 Department of Chemical Pathology, Alexandria University , Alexandria, Egypt .
authors.forename: Moyassar A
authors.initials: MA
authors.lastname: Zaki
authors.affiliation: 1 Department of Chemical Pathology, Alexandria University , Alexandria, Egypt .
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Awad
authors.affiliation: 2 Department of Internal Medicine, Medical Research Institute, Alexandria University , Alexandria, Egypt .
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: El-Ghalid
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D016147:Genes, Tumor Suppressor; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics* / Q000821:virology*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human