title: Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma.
abstract: BACKGROUND
  Circulating cell-free DNA is present in increased amounts in the blood of patients with one of several forms of cancer.
  
  
  METHODS
  A real-time PCR assay with glutathione S-transferase pi (GSTP1) gene was used to measure cell-free DNA levels in the sera of 52 patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), which included 30 HCV carriers without known HCC and 16 HCV-negative non-cancer patients (controls).
  
  
  RESULTS
  Cell-free DNA levels were significantly higher in the sera from HCC patients than in the sera from HCV carriers or the control subjects. Cell-free DNA levels were associated with the degree of tumor differentiation and size but not patient age, gender, TNM stage or levels of alpha-fetoprotein (AFP) or protein induced by vitamin K absence (PIVKA-II). The cell-free DNA assay had a sensitivity of 69.2% and a specificity of 93.3% in discriminating HCC and HCV carriers at the optimal cut-off value of 73.0 ng/ml, with an area of 0.90 (95% CI, 0.83-0.96) under the receiver operating characteristic curve. The discriminative power of cell-free DNA was superior to that of AFP or PIVKA-II.
  
  
  CONCLUSIONS
  Our results showed that levels of circulating cell-free DNA are significantly increased in sera of patients with HCV-associated HCC, suggesting that circulating cell-free DNA may be a good biomarker specific for HCV-associated HCC.
authors.affiliation: Department of Surgery II, Yamaguchi University Postgraduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505.
authors.forename: Norio
authors.initials: N
authors.lastname: Iizuka
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Toyoki
authors.initials: T
authors.lastname: Moribe
authors.forename: Nozomi
authors.initials: N
authors.lastname: Fujita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Miura
authors.forename: Markus
authors.initials: M
authors.lastname: Stark
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tamatsukuri
authors.forename: Hideo
authors.initials: H
authors.lastname: Ishitsuka
authors.forename: Koichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Takao
authors.initials: T
authors.lastname: Tamesa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics / Q000821:virology; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000097:blood* / Q000150:complications / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm