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ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma

  • Authors:
    • Ryouichi Tsunedomi
    • Norio Iizuka
    • Kiyoshi Yoshimura
    • Michihisa Iida
    • Masahito Tsutsui
    • Noriaki Hashimoto
    • Shinsuke Kanekiyo
    • Kazuhiko Sakamoto
    • Takao Tamesa
    • Masaaki Oka
  • View Affiliations / Copyright

    Affiliations: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Complementary Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
    Copyright: © Tsunedomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1551-1559
    |
    Published online on: March 8, 2013
       https://doi.org/10.3892/ijo.2013.1854
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Abstract

The poor prognosis of hepatocellular carcinoma (HCC) can be explained largely by the high rate of intrahepatic recurrence (IHR). Identification of genes related to IHR is needed to improve the poor prognosis and important for personalized medicine. Eighty-one HCC specimens were used in this study. We screened for IHR-related genes by DNA microarray analysis. The validation of screening was performed by using real-time PCR. The methylation levels in genomic DNAs were measured by quantitative methylation-specific PCR. Six hepatoma cell lines were used for examination of ABCB6 expressional regulation. Time-to-event analyses for recurrence after surgery were analyzed by Kaplan-Meier analysis and Cox regression analysis with cutoff values obtained from receiver operating characteristic (ROC) analysis. We confirmed that ABCB6 mRNA levels were signi­ficantly higher in hepatitis C virus (HCV)-related HCCs with early IHR compared to HCV-related HCCs without early IHR (2.5-fold, P=0.01) and the corresponding non-cancerous livers (3.1-fold, P=0.05). Experiments with cell lines showed correlation between DNA methylation and mRNA levels of ABCB6. ROC analysis revealed that mRNA levels (0.81 area under the curve, 88% sensitivity and 72% specificity) and DNA methylation levels (0.81 area under the curve, 80% sensitivity and 80% specificity) of ABCB6 in HCV-related HCCs allowed for the accurate discrimination of the development of early IHR. Cox regression analysis revealed that ABCB6 mRNA levels was an independent risk factor for IHR of HCV-related HCC. Aberrant mRNA and DNA methylation levels of ABCB6 may serve as useful predictive biomarkers for early IHR of HCV-related HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Tsunedomi R, Iizuka N, Yoshimura K, Iida M, Tsutsui M, Hashimoto N, Kanekiyo S, Sakamoto K, Tamesa T, Oka M, Oka M, et al: ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma. Int J Oncol 42: 1551-1559, 2013.
APA
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N. ... Oka, M. (2013). ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma. International Journal of Oncology, 42, 1551-1559. https://doi.org/10.3892/ijo.2013.1854
MLA
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N., Kanekiyo, S., Sakamoto, K., Tamesa, T., Oka, M."ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma". International Journal of Oncology 42.5 (2013): 1551-1559.
Chicago
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N., Kanekiyo, S., Sakamoto, K., Tamesa, T., Oka, M."ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma". International Journal of Oncology 42, no. 5 (2013): 1551-1559. https://doi.org/10.3892/ijo.2013.1854
Copy and paste a formatted citation
x
Spandidos Publications style
Tsunedomi R, Iizuka N, Yoshimura K, Iida M, Tsutsui M, Hashimoto N, Kanekiyo S, Sakamoto K, Tamesa T, Oka M, Oka M, et al: ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma. Int J Oncol 42: 1551-1559, 2013.
APA
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N. ... Oka, M. (2013). ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma. International Journal of Oncology, 42, 1551-1559. https://doi.org/10.3892/ijo.2013.1854
MLA
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N., Kanekiyo, S., Sakamoto, K., Tamesa, T., Oka, M."ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma". International Journal of Oncology 42.5 (2013): 1551-1559.
Chicago
Tsunedomi, R., Iizuka, N., Yoshimura, K., Iida, M., Tsutsui, M., Hashimoto, N., Kanekiyo, S., Sakamoto, K., Tamesa, T., Oka, M."ABCB6 mRNA and DNA methylation levels serve as useful biomarkers for prediction of early intrahepatic recurrence of hepatitis C virus-related hepatocellular carcinoma". International Journal of Oncology 42, no. 5 (2013): 1551-1559. https://doi.org/10.3892/ijo.2013.1854
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