Abstract
Background
The aim of this study was to evaluate the prognostic value of the Jagged-1/Notch-1 expression in patients with head and neck carcinoma and to examine the possible role of the Jagged-1/Notch-1 signaling in tumorigenesis.
Methods
Immunohistochemical staining was performed on 59 formalin-fixed, paraffin-embedded head and neck carcinoma surgical specimens for Jagged-1 and Notch-1 expression. The head and neck cancer cell line, Fadu, with or without ectopic expression of the intracellular domain of Notch-1 (NICD) was also used for examining the tumorigenic capacity in vitro and in vivo.
Results
The study included 59 patients with a median age of 54 years (range, 35–73 years). Patients harboring tumors with both high-level Jagged-1 (J1Hi) and high-level Notch-1 (N1Hi) had a worse overall survival than the patients only with J1Hi or N1Hi as well as the patients with low-level Jagged-1 and Notch-1 (J1Lo/N1Lo) (P < 0.001). The 5-year survival rate and the median survival time were 5% and 10.9 months for J1Hi/N1Hi patients, while they were 35.04% and 47.7 months for non-J1Hi/NiHi patients. Ectopic expression of the active Notch-1 (NICD) in Fadu cells greatly enhanced cell migration and invasiveness in vitro and tumorigenic capacity in vivo.
Conclusions
High-level coexpression of Jagged-1 and Notch-1 is associated with poor overall survival in patients with head and neck cancer. Constitutive activation of the Notch signaling, which is possibly initiated by the direct interaction between Jagged-1 and Notch-1 in head and neck cancer, confers tumor cells with a more aggressive phenotype.
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Acknowledgment
We thank Ming-Chu Lu for technical assistance. This work and another related study, “Prognostic value of CD44 mRNA of peripheral blood in patients with locally advanced head and neck cancers,” were supported by the National Science Council (grant 96-2314-B-182A-026-My3) and the grant from Chang Gung Memorial Hospital (NMRPG 666012). The authors report no conflict of interest.
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Lin, JT., Chen, MK., Yeh, KT. et al. Association of High Levels of Jagged-1 and Notch-1 Expression with Poor Prognosis in Head and Neck Cancer. Ann Surg Oncol 17, 2976–2983 (2010). https://doi.org/10.1245/s10434-010-1118-9
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DOI: https://doi.org/10.1245/s10434-010-1118-9