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DNA amplification and expression of FADD in oral squamous cell carcinoma
Chanwit Prapinjumrune1, Kei-ichi Morita, Yuri Kuribayashi
1Oral and Maxillofacial Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Background:
The Fas-associated death domain-containing protein, FADD, is an adaptor for relaying apoptotic signals. However, recent studies have shown that FADD also plays an important role in the growth and regulation of the cell cycle. The purpose of this study was to elucidate the role of FADD in oral squamous cell carcinoma (SCC).
Methods:
The DNA amplification of FADD from 30 samples of tongue SCC was analyzed using real-time PCR and the protein expression of FADD from 60 samples of tongue SCC was analyzed using immunohistochemistry.
Results:
The DNA amplifications of FADD were observed in 13 cases (44.3%) and were significantly correlated with the histopathological differentiation grade of SCCs (P = 0.009). FADD expression levels compared with the matched adjacent epithelium increased significantly (P = 0.000). Additionally, the positive expressions of FADD were significantly correlated with lymph node metastasis of SCCs (P = 0.029) and the 5-year disease-specific survival rates (P = 0.049). A positive association between FADD expression level and the histopathological differentiation grade was found to be limited to T1 SCCs (P = 0.019). DNA amplification was moderately correlated (correlation coefficient = 0.406, P = 0.026) with expression of FADD in 30 samples of tongue SCC.
Conclusion:
In tongue SCCs, the expression of FADD was higher when compared with that of adjacent areas, which might be determined via genomic amplification in 11q13.3. Thus, SCC cells with the expression of FADD are possibly more likely to become metastatic and to worsen survival rates.
Insights
Fas-associated death domain-containing protein (FADD) expression is elevated in tongue squamous cell carcinoma (SCC), correlating with poorer survival and increased metastasis. This may be driven by genomic amplification.
Area of Science:
- Molecular biology
- Oncology
- Cell biology
Background:
- Fas-associated death domain-containing protein (FADD) is crucial for apoptosis.
- Emerging evidence highlights FADD's role in cell cycle regulation and growth.
- The function of FADD in oral squamous cell carcinoma (SCC) requires further investigation.
Purpose of the Study:
- To investigate the role of FADD in the development and progression of oral squamous cell carcinoma (SCC).
Main Methods:
- Real-time PCR was used to analyze FADD DNA amplification in 30 tongue SCC samples.
- Immunohistochemistry assessed FADD protein expression in 60 tongue SCC samples.
- Correlations between FADD DNA/protein levels and clinicopathological features were examined.
Main Results:
- FADD DNA amplification occurred in 44.3% of SCCs, linked to differentiation grade (P=0.009).
- FADD protein expression was significantly higher in SCC compared to adjacent epithelium (P=0.000).
- Elevated FADD expression correlated with lymph node metastasis (P=0.029) and reduced 5-year survival (P=0.049).
Conclusions:
- Increased FADD expression in tongue SCC, potentially due to 11q13.3 genomic amplification, is associated with adverse outcomes.
- Higher FADD levels may predict metastatic potential and poorer survival in SCC patients.
- FADD's role extends beyond apoptosis to influencing SCC progression.
