LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer.
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.
Pattamadilok
J
J
Department of Obstetrics and Gynecology, Chulalongkorn University, Bangkok, Thailand.
Huapai
N
N
Rattanatanyong
P
P
Vasurattana
A
A
Triratanachat
S
S
Tresukosol
D
D
Mutirangura
A
A
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
D014408:Biomarkers, Tumor