title: Hepatocellular carcinoma suppressor 1 promoter hypermethylation in serum. A diagnostic and prognostic study in hepatitis B.
abstract: BACKGROUND
  Liver cancer ranks as the second leading cause of cancer-related mortality in man worldwide, and hepatocellular carcinoma (HCC) is the most prevalent malignant neoplasm of the liver. The sensitivity of alpha-fetoprotein (AFP) as an HCC diagnostic marker for HCC diagnosis is 39-65%, and one-third patients with HCC are missed using AFP. New biomarkers are needed to diagnose HCC at an earlier stage and to individualize treatment strategies. Hepatocellular carcinoma suppressor 1 (HCCS1) is a newly identified liver tumor suppressor gene.
  
  
  OBJECTIVE
  Our study evaluated the diagnostic value of serum HCCS1 promoter methylation in patients with HCC associated with hepatitis B.
  
  
  METHODS
  We determined the methylation status of serum HCCS1 promoter in 120 patients with HCC, 146 patients with chronic hepatitis B (CHB) and 27 healthy controls (HCs) by methylation-specific polymerase chain reaction (MSP). Evaluation of a cohort with 63 patients with HCC and 44 patients with CHB was set as a validation dataset.
  
  
  RESULTS
  The frequency of HCCS1 promoter methylation in patients with HCC was significantly higher than that in patients with CHB (P<0.001) and HCs (P<0.001), and was associated with tumor node-metastasis (TNM) stage (P=0.01). The sensitivity of serum HCCS1 promoter methylation for discriminating patients with HCC from CHB was 62.5% and that of AFP alone was 55%. Notably, the sensitivity of serum HCCS1 promoter methylation plus AFP level was 81.7%.
  
  
  CONCLUSIONS
  HCCS1 has potential as a biomarker for diagnosis and prognosis of patients with HCC.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tian
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 Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Ze-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China.
authors.forename: Long-Yan
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China. Electronic address: wangdoc876@126.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics* / Q000821:virology; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015203:Reproducibility of Results; D033921:Vesicular Transport Proteins / Q000097:blood / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C503307:VPS53 protein, human; D033921:Vesicular Transport Proteins; D000509:alpha-Fetoproteins; D004247:DNA