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Published on: January 12, 2020
Protein expression of Notch-1 and Notch-3 behaves differently in oral squamous cell carcinoma
Trupti I Trivedi1, Priti P Trivedi2
1Cancer Biology Department, Molecular Diagnostics and Research Lab 1, Ahmedabad, Gujarat, India.
Objective:
Depending on cell context, aberrant expression of Notch-1 and Notch-3 can employ either tumor suppressive or oncogenic roles. However, their roles in oral squamous cell carcinoma (OSCC) remain unclear, particularly in Indian population due to lack of availability of data from India. Therefore, we sought to explore the roles of Notch-1 and Notch-3 in OSCC and to investigate their influence on the disease outcome of patients.
Materials And Method:
Protein expression of Notch-1 and Notch-3 were localized immunohistochemically in 120 pre-therapeutic OSCC patients and assessed for their roles in disease outcomes.
Results:
Protein expressions of Notch-1 and Notch-3 were detected in 54% and 61% of patients, respectively. Notch-1 was found to be significantly negatively associated with tumor size ( P = 0.009), nodal status ( P = 0.045), and disease stage ( P = 0.003). Contradictorily, the expression of Notch-3 was found to be positively correlated with tumor size ( P = 0.003), nodal status ( P = 0.012), and disease stage ( P = 0.001). In a Cox multivariate analysis, Notch-1 ( P = 0.037) acts as an independent favorable prognosticator for disease-free survival (DFS). For overall survival (OS), Notch-3 ( P = 0.006) remained an unfavorable prognostic parameter for predicting worse OS.
Conclusion:
Notch-1 and Notch-3 are useful prognosticators; however, Notch-1 acts as a tumor suppressor, whereas, Notch-3 acts as an oncogene correlating with aggressive phenotype. Therefore, it is very important to study both markers for OSCC patients to add prognostic information and thereby help guide therapeutic decisions.
Insights
Notch-1 acts as a tumor suppressor in oral squamous cell carcinoma (OSCC), improving disease-free survival. Conversely, Notch-3 acts as an oncogene, correlating with aggressive OSCC and worse overall survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant Notch signaling pathway component expression can be tumor suppressive or oncogenic.
- The specific roles of Notch-1 and Notch-3 in oral squamous cell carcinoma (OSCC) are not well-defined, especially in the Indian population.
- Understanding these roles is crucial for prognostic assessment and therapeutic strategies in OSCC.
Purpose of the Study:
- To investigate the expression and prognostic significance of Notch-1 and Notch-3 in oral squamous cell carcinoma (OSCC).
- To determine the association of Notch-1 and Notch-3 expression with clinicopathological parameters and patient outcomes in OSCC.
Main Methods:
- Immunohistochemical localization of Notch-1 and Notch-3 protein expression.
- Analysis of 120 pre-therapeutic oral squamous cell carcinoma (OSCC) patient samples.
- Correlation of protein expression with tumor size, nodal status, disease stage, disease-free survival (DFS), and overall survival (OS) using Cox multivariate analysis.
Main Results:
- Notch-1 and Notch-3 protein expression was detected in 54% and 61% of OSCC patients, respectively.
- Notch-1 expression was negatively associated with tumor size, nodal status, and disease stage, indicating a tumor-suppressive role.
- Notch-3 expression was positively correlated with tumor size, nodal status, and disease stage, suggesting an oncogenic role. Notch-1 was an independent favorable prognosticator for DFS, while Notch-3 was an unfavorable prognosticator for OS.
Conclusions:
- Notch-1 functions as a tumor suppressor in OSCC, associated with better disease-free survival.
- Notch-3 acts as an oncogene in OSCC, linked to an aggressive phenotype and poorer overall survival.
- Evaluating both Notch-1 and Notch-3 expression provides valuable prognostic information for guiding therapeutic decisions in OSCC patients.
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