Methylation status of WWOX gene promoter CpG islands in epithelial ovarian cancer and its clinical significance

Abstract

WW domain-containing oxidoreductase (WWOX) is a newly identified tumor suppressor gene that is associated with abnormal DNA methylation. The aim of this study was to evaluate the methylation status of CpG islands in the WWOX gene promoter region in cases of epithelial ovarian cancer and explore the correlation between the methylation status of the WWOX gene CpG islands and clinicopathological indices in patients with epithelial ovarian cancer. The methylation status of the WWOX gene CpG island was evaluated by methylation-specific polymerase chain reaction (MSP) in 48 patients with epithelial ovarian cancer, 18 patients with borderline epithelial ovarian tumors, 26 patients with epithelial benign tumors and 33 patients with normal ovarian tissues. Results showed that the rates of CpG island methylation in the WWOX gene promoter region in epithelial ovarian cancer tissues, borderline ovarian tumor tissues and benign ovarian tumor tissues were 43.75, 26.32 and 3.84%, respectively. The WWOX gene CpG islands were not methylated in normal ovarian tissues. The rate of CpG island methylation in epithelial ovarian cancer tissues was higher than that of other ovarian tissues and these differences were found to be statistically significant (P<0.01). The rate of CpG island methylation in the WWOX gene promoter region in late-stage (stage III and IV) epithelial ovarian cancer tissues was higher than that of early-stage (stage I and II) epithelial ovarian cancer tissues, and these differences were found to be statistically significant (P<0.05). In conclusion, epithelial ovarian cancer tissues showed CpG island hypermethylation in the WWOX gene promoter region, which may be an important mechanism leading to WWOX gene inactivation. Atypical methylation of WWOX gene is associated with the formation and progression of epithelial ovarian cancer, rendering it a potentially important indicator in the early diagnosis and prognosis of epithelial ovarian cancer.