Expression of Jagged1/Notch3 Signaling Pathway and their Relationship with the Tumor Angiogenesis in TNBC

Background and aims: Jagged1/Notch3 signaling pathway plays a key role in angiogenesis of breast cancer, but little is known in TNBC. This study was designed to investigate the expression of Jagged1/Notch3 mRNA and protein in TNBC, analyze their correlations with clinicopathological characteristics and prognosis. Moreover, the interrelationship among Jagged1/Notch3 and VEGF was initially evaluated.

Methods: Jagged1/Notch3 mRNA and protein expression levels were determined by Q-RT-PCR and Western blotting. Additionally, Immunohistochemistry for Jagged1/Notch3 was detected by Ventana platform, VEGF and CD34 was performed using the EnVision/HRP technique.

Results: mRNA transcriptionof Jagged1/Notch3 was in accord with protein expression. TNBC patients with positive Jagged1 expression had poorer DFS (p = 0.008) and OS (p = 0.004). Jagged1 expression was independent predictors of OS (p = 0.038). The expression of VEGF was positively correlative to MVD (p = 0.018), MVD was significantly associated with Jagged1 (p <0.0001) and Notch3 (p <0.0001). The expression of Jagged1/Notch3 has no correlation with VEGF, only in positive VEGF expression of TNBC patients Jagged1/Notch3 had influence on DFS and OS (p <0.05).

Conclusion: Jagged1/Notch3 was -expressed at both the mRNA and protein levels, Jagged1 served as an independent predictor of poor prognosis. We speculate that there is a cross-talk between Jagged1/Notch3 and VEGF in TNBC angiogenesis. Jagged1/Notch3 is expected to be an important signaling pathway for TNBC progression and a potential target for TNBC neovascularization therapy.