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Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma

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Abstract

Background

DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown.

Aims

The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance.

Methods

Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs).

Results

Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC.

Conclusions

Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC.

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Acknowledgments

This work was supported by grants from the Science and Technology Development Plan of Shandong Province (2014GSF118068), the National Natural Science Foundation of China (81171579, 81201287, 81371832), and the Key Project of Chinese Ministry of Science and Technology (2012ZX10002007, 2013ZX10002001).

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Authors and Affiliations

  1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China

    Cheng-Yun Dou, Yu-Chen Fan, Yang Yang & Kai Wang

  2. Institute of Hepatology, Shandong University, Jinan, 250012, China

    Yu-Chen Fan & Kai Wang

  3. Department of Pathology, The First Affiliated Hospital of Sun Yat-san University, Guangzhou, 510080, China

    Chuang-Jie Cao

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  1. Cheng-Yun Dou
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  4. Yang Yang
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  5. Kai Wang
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Correspondence to Kai Wang.

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Dou, CY., Fan, YC., Cao, CJ. et al. Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma. Dig Dis Sci 61, 1130–1138 (2016). https://doi.org/10.1007/s10620-015-3975-3

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  • DOI: https://doi.org/10.1007/s10620-015-3975-3

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