Molecular Diagnostics

British Journal of Cancer (2007) 97, 1399–1403. doi:10.1038/sj.bjc.6604034 www.bjcancer.com
Published online 16 October 2007

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma

Y Tokuhisa1, N Iizuka1,2, I Sakaida3, T Moribe4, N Fujita4, T Miura4, S Tamatsukuri4, H Ishitsuka4, K Uchida3, S Terai3, K Sakamoto1, T Tamesa1 and M Oka1

  1. 1Department of Surgery II, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
  2. 2Department of Complementary Medicine, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
  3. 3Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan
  4. 4Molecular Diagnostics R&D Department, Molecular Diagnostics Division, Roche Diagnostics K.K., 6-1, Shiba 2-chome, Minato-ku, Tokyo 105-0014, Japan

Correspondence: Dr M Oka, E-mail: 2geka-1@po.cc.yamaguchi-u.ac.jp

Received 12 June 2007; Revised 12 September 2007; Accepted 24 September 2007; Published online 16 October 2007.

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Abstract

In a previous study, we showed that levels of cell-free DNA (cfDNA) were significantly higher in sera of patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) than in sera of non-HCC patients with HCV. To confirm this finding, we analysed serum cfDNA levels in a cohort of 96 patients with HCV-related HCC and in 100 HCV carriers without known HCC. Again we found that serum cfDNA levels were significantly higher in HCC patients than in HCV carriers (115.9plusminus98.3 vs 34.4plusminus40.4 ng ml-1 (meanplusminuss.d.), P<0.0001). Of 87 eligible patients who underwent curative hepatectomy, those with a high cfDNA level had a significantly shorter overall survival (OS) time than those in whom the cfDNA level was not high. Cox proportional hazards model showed the cfDNA level to be an independent prognostic factor for OS and cancer recurrence in distant organs. Our results suggest that the serum cfDNA level reflects the metastatic potential of HCV-related HCC and that it can be a useful predictive biomarker for distant metastasis after curative surgery.

Keywords:

HCV, HCC, blood testing, cell-free DNA, real-time PCR, GSTP1

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