title: Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Dou
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China.|Institute of Hepatology, Shandong University, Jinan, 250012, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-san University, Guangzhou, 510080, China.
authors.forename: Chuang-Jie
authors.initials: CJ
authors.lastname: Cao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. wangdoc876@126.com.|Institute of Hepatology, Shandong University, Jinan, 250012, China. wangdoc876@126.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015415:Biomarkers / Q000097:blood*; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D042241:Early Diagnosis; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D000509:alpha-Fetoproteins / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D004248:DNA (Cytosine-5-)-Methyltransferases; D047628:Estrogen Receptor alpha; D000509:alpha-Fetoproteins; D000097584:DNA Methyltransferase 3B; C513384:CDH1 protein, human; C506487:ESR1 protein, human
keywords: CDH1; DNMT3b; ESR1; HBV-related HCC; Methylation