title: Circulating miRNA-122, miRNA-199a, and miRNA-16 as Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. Having a very poor prognosis, it currently ranks as the third most common cause of cancer-related deaths. MiRNAs are a set of small, single-stranded, non-coding RNA molecules that negatively regulate gene expression at the post-transcriptional level. Several miRNAs were found to be frequently deregulated in HCC.
  
  
  OBJECTIVE
  To investigate whether miRNA-122, miRNA-199a, and miRNA-16 are altered in sera of hepatitis C virus (HCV)-induced HCC patients compared with chronic HCV patients without HCC, and to assess their diagnostic value to differentiate between HCC and chronic HCV in order to develop a non-invasive diagnostic and prognostic tool for HCC.
  
  
  METHODS
  We analysed the expression of mature miRNA-122, miRNA-199a, and miRNA-16 in serum by a singleplex TaqMan two-step stem loop quantitative real-time reverse-transcription PCR (qRT-PCR) in 40 newly diagnosed HCC patients and 40 chronic HCV liver cirrhosis patients, as well as 20 apparently healthy individuals as a control group, using RNU48 as a normalisation control.
  
  
  RESULTS
  Serum miR-16 was significantly lower in HCC than in HCV patients (P = 0.033). The serum level of miR-199a in chronic HCV patients was significantly lower than in healthy controls (P = 0.001). Receiver operating curve (ROC) analysis for serum miRNA-16 for discriminating HCC from HCV patients showed that at the cut-off value of 0.904, the sensitivity and specificity for this marker were 57.5 and 70 %, respectively. The combination of serum miR-16 with serum alpha fetoprotein (AFP) resulted in improved sensitivity to 85% and increased diagnostic accuracy to 87.5 %. Serum miR-199a and miR-16 were significantly associated with several parameters of HCC such as tumour size and number.
  
  
  CONCLUSIONS
  The combination of serum miR-16 and serum AFP is a significant improvement on the current best practice of serum AFP for HCC in HCVpositive patients. Serum miR-199a and miR-16 could be used as potential indicators of the progress of HCC.
authors.affiliation: Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt, nevineelabd@yahoo.com.
authors.forename: Nevine E
authors.initials: NE
authors.lastname: El-Abd
authors.forename: Nahla A
authors.initials: NA
authors.lastname: Fawzy
authors.forename: Suzan M
authors.initials: SM
authors.lastname: El-Sheikh
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Soliman
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000150:complications / Q000235:genetics; D055088:Early Detection of Cancer; D004534:Egypt; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000150:complications / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C531907:MIRN122 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D000509:alpha-Fetoproteins; C531408:mirn199 microRNA, human