title: LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis.
abstract: BACKGROUND
  Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear.
  
  
  METHODS
  Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables.
  
  
  RESULTS
  Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25).
  
  
  CONCLUSIONS
  LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Shigaki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Asuka
authors.initials: A
authors.lastname: Murata
authors.forename: Shiro
authors.initials: S
authors.lastname: Iwagami
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D042822:Genomic Instability; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D013447:Sulfites / Q000737:chemistry*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D013447:Sulfites; C009279:sodium bisulfite