Association of high levels of Jagged-1 and Notch-1 expression with poor prognosis in head and neck cancer

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 (J1(Hi)) and high-level Notch-1 (N1(Hi)) had a worse overall survival than the patients only with J1(Hi) or N1(Hi) as well as the patients with low-level Jagged-1 and Notch-1 (J1(Lo)/N1(Lo)) (P < 0.001). The 5-year survival rate and the median survival time were 5% and 10.9 months for J1(Hi)/N1(Hi) patients, while they were 35.04% and 47.7 months for non-J1(Hi)/Ni(Hi) 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.