title: DNA methylation markers and serum α-fetoprotein level are prognostic factors in hepatocellular carcinoma.
abstract: BACKGROUND
  Hypermethylation of relevant genes may affect the prognosis of patients with cancer. The purpose of this study was to analyze whether methylation of the promoter regions of cell cycle regulators as well as elevated α-Fetoprotein (AFP) levels are useful prognostic factors for patients with hepatocellular carcinoma (HCC).
  
  
  METHODS
  Nested methylation-specific PCR (nested-MSP) was used to analyze methylation status of the promoter regions of p15, p16, p21, p27, and ras-association domain family 1 (RASSF1A) genes in tumor specimens from 50 patients with HCC.
  
  
  RESULTS
  Promoter methylation was most common in the RASSF1A gene (96%), followed by the p16 gene (56%), the p21 gene (44%), the p15 gene (28%), and the p27 gene (2%). Patients with a serum AFP level < 400 ng/mL and an unmethylated p21 promoter had a better prognosis than patients with a serum AFP level ≥ 400 ng/mL and a methylated p21 promoter (overall survival, p = 0.076; disease-free survival, p = 0.016). In addition, patients with full methylation of the promoter region of RASSF1A had a better prognosis than patients with a partially methylated or unmethylated RASSF1A promoter region if their serum AFP level was ≥ 400 ng/mL (overall survival, p = 0.028; disease-free survival, p = 0.078).
  
  
  CONCLUSIONS
  A partially methylated or unmethylated RASSF1A promoter as well as elevated serum AFP level or methylation of p21 in addition to elevated serum AFP level might be associated with poor prognosis in patients with hepatocellular carcinoma.
authors.affiliation: Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Jin-Ching
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Yao-Chung
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Cheng-Chung
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Biology, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Pei-Yin
authors.initials: PY
authors.lastname: Shih
authors.affiliation: Department of Nursing, Hung Kuang University, Taichung, Taiwan.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Department of Biology, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Chien
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000509:alpha-Fetoproteins