title: Hypomethylation of long interspersed nuclear element-1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma.
abstract: BACKGROUND
  Epigenetic alterations are well documented in hepatocarcinogenesis. However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter and its relationship with clinicopathological features in hepatocellular carcinoma(HCC) remain unknown.
  
  
  METHODS
  The bisulfite-specific PCR and DNA sequencing analysis was performed to assess the methylation status of LINE-1 promoter in a pilot cohort of 71 patients with HCC. Additionally,methylation levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by real-time PCR and compared with clinicopathological parameters in a cohort of 172 HCC. All the patients included were in BCLC stage A or B.
  
  
  RESULTS
  Most patients with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV-related cirrhosis and normal controls (P < 0.001). The HCC patients with LINE-1 promoter hypomethylation had a median tumour-free survival (TFS) and overall survival (OS)post-resection of 22.0 (95% CI: 13.3–30.7) months and 35.0 (95% CI: 24.0–46.1) months, respectively, compared with 40 months and ~60 months for those with LINE-1 promoter hypermethylation (P < 0.05). Multivariate analyses showed that the hypomethylation level at CpG site 7 and 18 of LINE-1 promoter, along with tumour size and tumour differentiation, was independently associated with both TFS and OS for patients with HCC after resection.
  
  
  CONCLUSIONS
  Promoter hypomethylation of LINE-1, especially at the CpG site 7 and 18, was associated with a poor prognosis in HCC.
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Gao
authors.forename: Jian-hui
authors.initials: JH
authors.lastname: Qu
authors.forename: Xiu-juan
authors.initials: XJ
authors.lastname: Chang
authors.forename: Yin-ying
authors.initials: YY
authors.lastname: Lu
authors.forename: Wen-lin
authors.initials: WL
authors.lastname: Bai
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Zhong-xian
authors.initials: ZX
authors.lastname: Xu
authors.forename: Lin-jing
authors.initials: LJ
authors.lastname: An
authors.forename: Chun-ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Yong-ping
authors.initials: YP
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult