title: CpG island methylator phenotype in plasma is associated with hepatocellular carcinoma prognosis.
abstract: OBJECTIVE
  To evaluate the clinical significance of CpG island methylator phenotype (CIMP) in plasma and its association with hepatocellular carcinoma (HCC) progress.
  
  
  METHODS
  CIMP status of 108 HCC patients was analyzed using a methylation marker panel in tumor tissues and plasma with methylation-specific polymerase chain reaction. Fifteen samples of non-neoplastic liver tissues and 60 of plasma from healthy persons were examined simultaneously. Examined genes included APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad.
  
  
  RESULTS
  The frequencies of high-level methylation in HCC tissue and plasma were at least 15% for the seven genes: APC, 48/108, 44.44% in tissue and 26/108, 24.07% in plasma; WIF-1, 53/108, 49.07% in tissue and 35/108, 32.41% in plasma; RUNX-3, 52/108, 48.14% in tissue and 42/108, 38.89% in plasma; DLC-1, 38/108, 35.18% in tissue and 23/108, 21.30% in plasma; SFRP-1, 40/108, 37.04% in tissue and 31/108, 28.7% in plasma; DKK, 39/108, 36.1% in tissue and 25/108, 23.14% in plasma; and E-cad, 37/108, 34.3% in tissue and 18/108, 16.67% in plasma. CIMP+ (≥ 3 methylated genes) was detected in 68 (60.2%) tumor tissue samples and 62 (57.4%) plasma samples. CIMP was not detected in non-neoplastic liver tissues or plasma of healthy persons. CIMP status in tumor tissues differed significantly in gender, hepatitis B surface antigen, alpha-fetoprotein, and tumor-node-metastasis stage (P < 0.05). Similar results were obtained with plasma samples (P < 0.05). There was no difference in CIMP status in age, presence of hepatitis C virus antibody, cirrhosis, number of nodes, number of tumors, tumor size, or Edmondson-Steiner stage. A one-year follow-up found that the metastatic rate and recurrence rate in the CIMP+ group were significantly higher than in the CIMP- group as assessed with plasma samples (P < 0.05).
  
  
  CONCLUSIONS
  Plasma DNA can be a reliable sample source for CIMP analysis. CIMP in plasma may serve as a molecular marker of late-stage and poor-prognosis HCC.
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China.
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Liu
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zhang
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Zhou
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Shi
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ke-Ping
authors.initials: KP
authors.lastname: Chen
authors.forename: Fu-Lin
authors.initials: FL
authors.lastname: Qiang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D018899:CpG Islands; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA