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Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer
Coexpression of Notch-1 and vascular endothelial growth factor-A predicts poor survival
Article first published online: 24 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 24, pages 5676–5685, 15 December 2010
How to Cite
Donnem, T., Andersen, S., Al-Shibli, K., Al-Saad, S., Busund, L.-T. and Bremnes, R. M. (2010), Prognostic impact of Notch ligands and receptors in nonsmall cell lung cancer. Cancer, 116: 5676–5685. doi: 10.1002/cncr.25551
- Issue published online: 3 DEC 2010
- Article first published online: 24 AUG 2010
- Manuscript Accepted: 1 JUL 2010
- Manuscript Revised: 25 MAY 2010
- Manuscript Received: 26 FEB 2010
- nonsmall cell lung cancer;
- Delta-like ligand 4;
Notch signaling plays a key role in embryonic vascular development and angiogenesis. The authors aimed to study the prognostic role of the angiogenesis-related Notch ligands and receptors and investigate the prognostic impact of the coexpression of vascular endothelial growth factor-A (VEGF-A) and Notch signaling.
Tumor tissue samples from 335 resected patients with stage I to IIIA nonsmall cell lung cancer (NSCLC) were obtained, and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers Notch-1, Notch-4, Delta-like ligand 4 (DLL4), and Jagged-1.
There were 191 squamous cell carcinomas (SCCs), 113 adenocarcinomas (ACs), and 31 large cell carcinomas. In AC, low tumor cell Delta-like ligand 4 expression was an independent negative prognostic factor (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.4-6.3 [P = .006]), whereas high tumor cell Notch-1 expression was an independent negative prognostic factor (HR, 2.2; 95% CI, 1.2-4.1 [P<.001]). In SCC, low stromal Delta-like ligand 4 expression was an independent indicator of poor prognosis (HR, 3.3; 95% CI, 1.8-6.1 [P<.001]). The coexpression of Notch-1 and VEGF-A had a significant prognostic impact (P<.001). For Notch-1 and VEGF-A, low/low (n = 142) versus high/high (n = 35) expression resulted in 5-year survival rates of 69% and 32%, respectively.
Delta-like ligand 4 and Notch-1 are independent prognostic factors in NSCLC, but have diverse impacts in SCC and AC. The coexpression of tumor cell Notch-1/VEGF-A has a major impact on survival. Cancer 2010. © 2010 American Cancer Society.