Clinical significance of notch receptors, NPR3, and DLL-3 in pediatric and adult medulloblastoma patients

Objectives This study aimed to investigate the expression of key genes (Notch-1, Notch-2, Notch-3, Notch-4, DLL1, DLL3, and NPR3) in the Notch signaling pathway in medulloblastoma tumors, and explore their correlation with clinicopathological features, including patient survival outcomes. Material & Methods A total of 103 histologically confirmed medulloblastoma tumor samples were analyzed using quantitative Real-time polymerase chain rection (qPCR) to assess the expression levels of the seven Notch pathway genes. The relationship between gene expression and various clinicopathological parameters, including tumor location, patient age, gender, and risk group classification, was examined. Statistical analyses were performed using SPSS software, with p-values ≤ 0.05 considered statistically significant. Progression-free survival (PFS) and overall survival (OS) were also analyzed to determine the clinical impact of gene expression levels. Results The study revealed varying levels of upregulation for the Notch pathway genes in medulloblastoma tumors: Notch-1 (38%), Notch-2 (58%), Notch-3 (82%), Notch-4 (33%), DLL1 (69%), DLL3 (71%), and NPR3 (57%). Notably, Notch-3 expression was significantly associated with tumors located in the occipital region (p=0.04). A significant inverse correlation was found between high-risk patients and Notch-4 upregulation (p=0.05). DLL3 expression showed significant inverse correlations with gender (p=0.03) and risk group classification (p=0.04), but a positive correlation with the primary tumor site (p=0.003). NPR3 expression was inversely correlated with patient age (p=0.01). Furthermore, all Notch receptors and ligands demonstrated positive intercorrelations, suggesting a coordinated role in tumor biology. Survival analysis showed that patients in the average-risk group had significantly higher recurrence rates at both 12 and 24 months compared to high-risk patients (p<0.01). Notably, patients who received only radiotherapy post-surgery had lower recurrence rates and better survival outcomes, with significantly lower incidences of death at 12 months (p=0.005) and 24 months (p=0.03). Conclusion The findings highlight the potential clinical significance of Notch-3, Notch-4 receptors, and DLL3 as key biomarkers in medulloblastoma. These genes offer promising targets for developing more personalized and effective treatment strategies. Further research into their precise role in tumor progression and response to therapy is warranted.