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Wnt inhibitory factor 1 (WIF1) methylation and its association with clinical prognosis in patients with
Pei Liu1,2, Jacson K Shen1, Francis J Hornicek1
1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Abstract:
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 CpG 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. In this study, we found promoter methylated WIF1 in both CS cell lines (CS-1 and SW1353) and tumor tissues. Western blot analysis confirmed loss WIF1 expression and activation of Wnt pathway proteins (Wnt5a/b, LRP6, and Dvl2). 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 survival curves and log-rank tests revealed that high levels of WIF1 methylation were associated with lower OS and PFS rates (p < 0.05). Multivariate Cox hazard analysis suggested that detection of high level methylation of WIF1 could be an independent prognostic factor in OS and PFS. In conclusion, 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.
Insights
Wnt inhibitory factor 1 (WIF1) promoter methylation silences WIF1 in chondrosarcoma (CS), a rare bone cancer. High WIF1 methylation correlates with poorer survival, suggesting it as a prognostic marker for CS patients.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Chondrosarcoma (CS) is a rare but aggressive bone cancer resistant to standard treatments.
- Aberrant DNA methylation of Wnt inhibitory factor 1 (WIF1) is implicated in various cancers.
- The role of WIF1 methylation in CS progression and prognosis remains uninvestigated.
Purpose of the Study:
- To investigate the epigenetic silencing of WIF1 via promoter DNA methylation in chondrosarcoma.
- To determine the correlation between WIF1 methylation levels and patient survival outcomes.
- To evaluate WIF1 methylation as a potential prognostic biomarker for CS.
Main Methods:
- Analysis of WIF1 promoter methylation in CS cell lines and patient tumor tissues.
- Western blot to assess WIF1 expression and Wnt pathway activation.
- Kaplan-Meier survival analysis and Cox hazard modeling to correlate WIF1 methylation with overall survival (OS) and progression-free survival (PFS).
Main Results:
- WIF1 promoter methylation was detected in CS cell lines and tumor tissues.
- Loss of WIF1 expression and activation of Wnt pathway proteins were confirmed.
- High WIF1 methylation levels significantly correlated with reduced OS and PFS rates (p < 0.05).
- WIF1 methylation emerged as an independent prognostic factor for OS and PFS.
Conclusions:
- WIF1 is epigenetically silenced through promoter DNA methylation in chondrosarcoma.
- WIF1 methylation serves as a potential prognostic marker for predicting patient outcomes in CS.
- Further validation may establish WIF1 methylation as a clinical tool for CS prognosis.
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