Association of high levels of Jagged-1 and Notch-1 expression with poor prognosis in head and neck cancer.
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.
Department of Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
Jen-Tsun
JT
Lin
Mu-Kuan
MK
Chen
Kun-Tu
KT
Yeh
Cheng-Shyong
CS
Chang
Tung-Hao
TH
Chang
Chi-Yon
CY
Lin
Yi-Chuan
YC
Wu
Bi-Wen
BW
Su
Kuan-Der
KD
Lee
Pey-Jium
PJ
Chang
D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D051881:Receptor, Notch1 / Q000235:genetics*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D016019:Survival Analysis
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins