LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer

Int J Gynecol Cancer. Jul-Aug 2008;18(4):711-7. doi: 10.1111/j.1525-1438.2007.01117.x. Epub 2007 Oct 18.

Abstract

A genome-wide hypomethylation is a common and crucial event in cancer. This study was to evaluate common epithelial ovarian cancer (EOC) if long interspersed element-1 (LINE-1) repetitive sequences methylation levels are progressively decreased during multistage carcinogenesis and there are the correlation between LINE-1 methylation levels and clinicopathologic characteristics. A total of 59 pairs of microdissected EOC tissues obtained from patients with EOC were examined for the methylation levels of LINE-1 repetitive sequences by a COBRALINE-1 (combined bisulfite restriction analysis of LINE-1) PCR protocol. The methylation levels were correlated with clinicopathologic parameters to determine the potential role of global hypomethylation as a prognostic marker for EOC. The LINE-1 methylation levels of 59 EOCs, 34.87 +/- 7.39%, were lower than in representative normal ovarian tissues (46.89 +/- 8.31%; 95% CI: 9.42-14.62; P < 0.001, paired-two-tailed t test). A decrease in the LINE-1 level of methylation was correlated with histological subtypes, higher FIGO and advanced tumor grade. Patients with greater hypomethylation (i.e., a methylation level <or=34.87%) had poorer mean overall survival (P = 0.003) and a lower mean progression-free interval (P < 0.001). Therefore, progressive decrease in LINE-1 methylation level is a common and important epigenetic process in ovarian multistep carcinogenesis. Moreover, the COBRALINE-1 method has the potential to be used as a tumor marker for EOC.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • DNA Methylation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Long Interspersed Nucleotide Elements / genetics*
  • Middle Aged
  • Molecular Diagnostic Techniques / methods
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Polymerase Chain Reaction / methods
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis

Substances

  • Biomarkers, Tumor