WIF1 Promoter Methylation Is Associated With Clinical Prognosis In Patients With Chondrosarcoma

Background Chondrosarcoma(CS)is a rare cancer,but it is the second most common primary malignant bone tumor and highly resistant to conventional chemotherapy and radiotherapy.Aberrant DNA methylation in the promoter Cp G island of Wnt inhibitory factor 1(WIF1)has been observed in different cancers.However,no studies have shown the relationship between WIF1 methylation and CS.Methods and Results In this study,we determined the methylation levels of WIF1 in CS cell lines(CS-1 and SW1353)and CS tissues.The results showed promoter methylated WIF1 in both CS cell lines and tumor tissues.Western blot analysis confirmed loss WIF1 expression and activation of Wnt pathway proteins(Wnt5a/b,LRP6,and Dvl2)in CS.We subsequently examined the correlation between levels of WIF1 methylation and overall survival(OS)and progression-free survival(PFS)in CS patient samples with a follow-up spanning 234 months(mean: 57.6 months).Kaplan-Meier survivalcurves and log-rank tests revealed that high levels of WIF1 methylation were associated with lower overall and progressive-free survival rates(p＜0.05).Multivariate Cox hazard analysis suggested that detection of high level methylation of WIF1 could be an independent prognostic factor in overall survival and progression-free survival.Conclusions We found that WIF1 is epigenetically silenced via promoter DNA methylation in CS and propose that WIF1 methylation may serve as a potential prognostic marker for patients with CS.