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Published on: January 12, 2020
Expression of Jagged1/Notch3 Signaling Pathway and their Relationship with the Tumor Angiogenesis in TNBC
Siliang Xue1, Lang He2, Xiao Zhang3
1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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.
Insights
Jagged1/Notch3 signaling is expressed in triple-negative breast cancer (TNBC). Jagged1 predicts poor prognosis, and Jagged1/Notch3 may be a therapeutic target for TNBC angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The Jagged1/Notch3 signaling pathway is crucial for breast cancer angiogenesis.
- Its role in triple-negative breast cancer (TNBC) remains largely uncharacterized.
- This study investigates Jagged1/Notch3 expression and its clinical significance in TNBC.
Purpose of the Study:
- To determine Jagged1/Notch3 mRNA and protein expression in TNBC.
- To analyze correlations between Jagged1/Notch3 and clinicopathological features, prognosis, and VEGF.
- To evaluate Jagged1/Notch3 as a potential therapeutic target in TNBC.
Main Methods:
- Quantitative real-time PCR (Q-RT-PCR) and Western blotting for mRNA and protein levels.
- Immunohistochemistry for Jagged1/Notch3, VEGF, and CD34 (microvessel density marker).
- Statistical analysis to assess correlations and prognostic significance.
Main Results:
- Jagged1/Notch3 mRNA and protein expression were concordant.
- Positive Jagged1 expression correlated with poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients.
- Jagged1 was an independent predictor of OS.
- VEGF expression correlated positively with microvessel density (MVD).
- MVD was significantly associated with both Jagged1 and Notch3 expression.
- Jagged1/Notch3 influenced DFS and OS in TNBC patients with positive VEGF expression.
Conclusions:
- Jagged1/Notch3 is expressed in TNBC at both mRNA and protein levels.
- Jagged1 serves as an independent predictor of poor prognosis in TNBC.
- A potential crosstalk exists between Jagged1/Notch3 and VEGF in TNBC angiogenesis.
- Jagged1/Notch3 represents a promising signaling pathway and therapeutic target for TNBC progression and neovascularization.
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