Association of High Levels of Jagged-1 and Notch-1 Expression with Poor Prognosis in Head and Neck Cancer
Association of High Levels of Jagged-1 and Notch-1 Expression with Poor Prognosis in Head and Neck Cancer
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DOI：
10.1245/s10434-010-1118-9
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发表时间：
2010-11-01
影响因子：
3.7
通讯作者：
Chang, Pey-Jium
中科院分区：
文献类型：
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作者：
Lin, Jen-Tsun;Chen, Mu-Kuan;Chang, Pey-Jium
背景。本研究的目的是评估Jagged-1/Notch-1在头颈部癌患者中的预后价值，并探讨Jagged-1/Notch-1信号在肿瘤发生中的可能作用。对59例经福尔马林固定、石蜡包埋的头颈部癌手术标本进行Jagged-1和Notch-1表达的免疫组化染色。同时，采用细胞内Notch-1 （NICD）结构域异位表达或不异位表达的头颈部癌细胞法度细胞系，在体外和体内检测其致瘤能力。该研究纳入59例患者，中位年龄54岁（范围35-73岁）。同时存在高水平jaged -1 （J1(Hi)）和高水平Notch-1 （N1(Hi)）的肿瘤患者的总生存率低于仅存在J1（Hi）或N1（Hi）的患者以及低水平jaged -1和Notch-1 (J1（Lo)/N1(Lo)）的患者（P < 0.001）。J1(Hi)/N1（Hi）患者的5年生存率为5%，中位生存时间为10.9个月，非J1(Hi)/Ni-Hi患者的5年生存率为35.04%，中位生存时间为47.7个月。在法度细胞中异位表达活性Notch-1 （NICD）可显著增强细胞在体外的迁移和侵袭性以及在体内的致瘤能力。Jagged-1和Notch-1的高水平共表达与头颈癌患者较差的总生存率相关。Notch信号的组成性激活，可能是由头颈癌中Jagged-1和Notch-1之间的直接相互作用启动的，赋予肿瘤细胞更具侵袭性的表型。
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. lmmunohistochemical 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.