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Updated: Aug 11, 2025

Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Hypermethylated WASF2: tumor suppressive role in head and neck squamous cell carcinoma
Jianyun Zhang1, Zhuang Ding1, Long Chen1
1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Background:
WASF2 regulates actin reorganization during cell migration. WASF2 has been identified as a regulator of the development of gastric cancer, breast cancer, and pancreatic cancer. But its regulatory mechanisms remain unknown. Also, its function was absent in head and neck squamous cell carcinoma (HNSCC). Consequently, we examined the effect of DNA methylation on aberrant WASF2 expression in HNSCC.
Methods:
TNMplot, TIMER, GSEA pathway analysis, and the Kaplan-Meier Plotter database were used to analyze the expression, function, and prognostic value of WASF2, as well as the correlation between WASF2 and infiltrating immune cells in HNSCC or pan-cancer analysis. WASF2 promoter methylation levels and the correlation between WASF2 expression and WASF2 promoter methylation in HNSCC were evaluated using the DNMIVD database. The effect of DNA methylation inhibitor on WASF2 expression was demonstrated in the GEO database. Finally, the TISIDB database determined the relationships between WASF2 methylation, immune cell infiltration, and immune inhibitors.
Results:
WASF2 was significantly downregulated in HNSCC tissues where WASF2 promoter methylation was elevated. According to the GEO database, treatment with a DNA methylation inhibitor notably restored the mRNA expression of WASF2. WASF2 expression was also a favorable indicator of human papilloma virus (HPV)-positive HNSCC. Its level of promoter methylation had detrimental effects on patient survival. In addition, patients with elevated levels of WASF2 demonstrated active G2/M regulation, TGF-β signaling, Kras signaling, fatty acid metabolism, and p53 pathways. WASF2 was positively associated with tumor-killing immune cells, while WASF2 methylation was positively related to immunosuppressive cells and immune-inhibitors.
Conclusions:
Hypermethylated WASF2 acted as a tumor suppressor of HNSCC by regulating tumor formation and immune imbalance.
Insights
Hypermethylated WASF2 acts as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC). DNA methylation inhibits WASF2 expression, impacting tumor formation and immune response in HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- The protein WASF2 is crucial for actin reorganization and cell migration.
- WASF2's role in gastric, breast, and pancreatic cancers is established, but its mechanisms and function in head and neck squamous cell carcinoma (HNSCC) are unknown.
- Investigating DNA methylation's effect on WASF2 expression in HNSCC is essential.
Purpose of the Study:
- To examine the impact of DNA methylation on aberrant WASF2 expression in HNSCC.
- To analyze the expression, function, and prognostic value of WASF2 in HNSCC.
- To explore the correlation between WASF2, immune cell infiltration, and methylation in HNSCC.
Main Methods:
- Utilized TNMplot, TIMER, GSEA, and Kaplan-Meier Plotter for expression and prognostic analysis.
- Assessed WASF2 promoter methylation and its correlation with expression using the DNMIVD database.
- Analyzed the effect of DNA methylation inhibitors on WASF2 expression via the GEO database and investigated immune relationships using TISIDB.
Main Results:
- WASF2 was significantly downregulated in HNSCC with elevated promoter methylation.
- DNA methylation inhibitor treatment restored WASF2 mRNA expression, indicating a regulatory role for methylation.
- WASF2 expression served as a favorable prognostic indicator in HPV-positive HNSCC, with promoter methylation negatively impacting survival.
Conclusions:
- Hypermethylated WASF2 functions as a tumor suppressor in HNSCC.
- WASF2 regulates tumor formation and immune imbalance in HNSCC.
- Restored WASF2 expression through methylation inhibition presents a potential therapeutic avenue.
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