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

Jen Tsun Lin, Mu Kuan Chen, Kun Tu Yeh, Cheng Shyong Chang, Tung Hao Chang, Chi Yon Lin, Yi Chuan Wu, Bi Wen Su, Kuan Der Lee, Pey Jium Chang

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51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2976-2983
Number of pages8
JournalAnnals of Surgical Oncology
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Oncology

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    Lin, J. T., Chen, M. K., Yeh, K. T., Chang, C. S., Chang, T. H., Lin, C. Y., Wu, Y. C., Su, B. W., Lee, K. D., & Chang, P. J. (2010). Association of high levels of Jagged-1 and Notch-1 expression with poor prognosis in head and neck cancer. Annals of Surgical Oncology, 17(11), 2976-2983. https://doi.org/10.1245/s10434-010-1118-9