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Association between HBV Pre-S mutations and the intracellular HBV DNAs in HBsAg-positive hepatocellular carcinoma in China

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Abstract

This study aimed to investigate the association between HBV mutations and intrahepatic HBV status and to determine the clinical features and the contribution of HBV mutations to postoperative prognosis for hepatocellular carcinoma (HCC) patients with HBsAg (+) in China. Using TaqMan fluorescent real-time PCR, HBV covalently closed circular DNA (cccDNA) and total DNA (tDNA) were both quantified in 106 pairs of tumor tissues (TT) and adjacent non-tumor tissues (ANTT) obtained from HCC patients who received no antiviral treatment before surgical treatment. The prevalence of 19 hot spot mutations was evaluated by Sanger sequencing. HBV cccDNA and tDNA were lower in TT than in ANTT. The loads of cccDNA and tDNA in ANTT were associated with serum HBV DNA and HBeAg. Three Pre-S mutants (A2962G and C2964A in Pre-S1 and C105T in Pre-S2) were associated with higher tumor cccDNA levels (P < 0.05), and A2962G/C2964A mutants were associated with higher AFP levels. This would assist to disclose the virological features, to implement a more clinically personalized therapy and to improve the prognosis of HBV-related HCC patients.

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Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

HBeAg:

Hepatitis e antigen

cccDNA:

Covalently closed circular DNA

tDNA:

Total DNA

TT:

Tumor tissues

ANTT:

Adjacent non-tumor tissues

BCP:

Basal core promoter

CP:

Core promoter

RT:

Reverse transcriptase

HR:

Hazard ratio

CI:

Confidence interval

DFS:

Disease-free survival

OS:

Overall survival

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Acknowledgments

This study was supported by China National Key Projects for Infectious Disease (No. 2012ZX10002-016); National Natural Science Foundation of China (Nos. 81271925, 81171664); Key Projects of Science and Technology Commission of Shanghai Municipality (11JC1416400).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, People’s Republic of China

    Hui Wang, Ai-Hua Wang, Meng Fang, Xing Gu, Qiang Ji & Chun-Fang Gao

  2. Wisplinghoff Medical Laboratories, Classen-Kappelmann-Str. 24, 50931, Cologne, Germany

    Olav A. Gressner

  3. Department of Hepatic Surgery (VI), Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China

    Shu-Qun Cheng

  4. Department of Hepatic Surgery (IV), Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, People’s Republic of China

    Feng Shen

Authors
  1. Hui Wang
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  2. Ai-Hua Wang
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  3. Olav A. Gressner
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  4. Meng Fang
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  5. Xing Gu
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  6. Qiang Ji
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  7. Shu-Qun Cheng
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  8. Feng Shen
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  9. Chun-Fang Gao
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Corresponding authors

Correspondence to Feng Shen or Chun-Fang Gao.

Additional information

Hui Wang and Ai-Hua Wang have contributed equally to this work.

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Wang, H., Wang, AH., Gressner, O.A. et al. Association between HBV Pre-S mutations and the intracellular HBV DNAs in HBsAg-positive hepatocellular carcinoma in China. Clin Exp Med 15, 483–491 (2015). https://doi.org/10.1007/s10238-014-0321-6

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  • DOI: https://doi.org/10.1007/s10238-014-0321-6

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