title: DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker in hepatocellular carcinoma.
abstract: BACKGROUND
  DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values.
  
  
  METHODS
  DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene.
  
  
  RESULTS
  Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050).
  
  
  CONCLUSIONS
  EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.
authors.affiliation: Departments of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hou
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Peng
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Hao
authors.forename: Jian-Peng
authors.initials: JP
authors.lastname: Cai
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Liang
authors.forename: Jing-Ming
authors.initials: JM
authors.lastname: Zhai
authors.forename: Kun-Song
authors.initials: KS
authors.lastname: Zhang
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Lai
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Yin
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger