title: Is serum level of methylated RASSF1A valuable in diagnosing hepatocellular carcinoma in patients with chronic viral hepatitis C?
abstract: OBJECTIVE
  The detection of the promoter hypermethylation of RASSF1A in serum DNA could be a valuable biomarker for early detection of preneoplastic lesions and early cancer development among high-risk populations who are at a high risk of hepatocellular carcinoma (HCC). Therefore, we aimed determining the serum level of methylated RASSF1A sequence in patients with chronic hepatitis C viral infection and to evaluate the predictive value of it as a diagnostic marker for HCC in patients with chronic hepatitis C viral infection.
  
  
  METHODS
  Serum levels of methylated RASSF1A were detected and measured using real-time PCR after digestion with a methylation-sensitive restriction enzyme in 40 patients with chronic HCV infection, 40 patients with HCC (on top of HCV) and 20 controls.
  
  
  RESULTS
  Methylated RASSF1A was detected in 10% of the controls, 62.5% of HCV group and in 90% of HCC group. Chronic HCV patients had insignificantly higher levels than the controls. The levels were significantly higher in patients with HCC compared to the controls (p=0.0001) and chronic HCV patients (p=0.001). By logistic regression analysis, the serum methylated RASSF1A was found to differentiate HCC patients from healthy controls with an AUROC of 0.83nmol/L, and an overall predictive accuracy of 77.5%. It was able to differentiate patients with HCC from those with chronic HCV infection alone with an AUROC of 0.733 and an overall predictive accuracy of 72.5%.
  
  
  CONCLUSIONS
  The mean serum levels of methylated RASSF1A could be of value for early diagnosis of HCC especially in high risk patients with HCV infection.
authors.affiliation: Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Postal Code 71515, Assiut, Egypt.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Mohamed
authors.forename: Eman M
authors.initials: EM
authors.lastname: Swify
authors.forename: Nabila F
authors.initials: NF
authors.lastname: Amin
authors.forename: Mona M
authors.initials: MM
authors.lastname: Soliman
authors.forename: Lubna M
authors.initials: LM
authors.lastname: Tag-Eldin
authors.forename: Nahla M
authors.initials: NM
authors.lastname: Elsherbiny
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000821:virology; D019175:DNA Methylation; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins