Elevated Levels of Circulating Cell-free DNA in the Blood of Patients with Hepatitis C Virus-associated Hepatocellular Carcinoma

• Published in: Anticancer research 2006-11, Vol.26 (6C), p.4713-4719
• Main Authors: IIZUKA, Norio, SAKAIDA, Isao, SAKAMOTO, Kazuhiko, TAMESA, Takao, OKA, Masaaki, MORIBE, Toyoki, FUJITA, Nozomi, MIURA, Toshiaki, STARK, Markus, TAMATSUKURI, Shigeru, ISHITSUKA, Hideo, UCHIDA, Koichi, TERAI, Shuji
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers, Tumor - blood; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; DNA, Neoplasm - blood; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepacivirus - isolation & purification; Hepatitis C - blood; Hepatitis C - complications; Hepatitis C - genetics; Hepatitis C virus; Humans; Liver Neoplasms - blood; Liver Neoplasms - genetics; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Tumors
• ISSN: 0250-7005; 1791-7530

Background: Circulating cell-free DNA is present in increased amounts in the blood of patients with one of several forms of cancer. Materials and 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. Conclusion: 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.