Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma.
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.
Iizuka
Norio
N
Department of Surgery II, Yamaguchi University Postgraduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505.
Sakaida
Isao
I
Moribe
Toyoki
T
Fujita
Nozomi
N
Miura
Toshiaki
T
Stark
Markus
M
Tamatsukuri
Shigeru
S
Ishitsuka
Hideo
H
Uchida
Koichi
K
Terai
Shuji
S
Sakamoto
Kazuhiko
K
Tamesa
Takao
T
Oka
Masaaki
M
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
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm