hes1-protein--human and Squamous-Cell-Carcinoma-of-Head-and-Neck

The Notch signaling pathway has been associated with the regulation of self-renewal capacity, cell cycle exit, and survival. However, the relationship between the Notch signaling pathway and HNSCC remains controversial.. A meta-analysis was conducted to evaluate the role of Notch signaling pathway in HNSCC.. Relevant studies published until March 31, 2015 were identified by searching the PubMed, EMBASE and Ovid database.. A total of 9 articles were eligible for this meta-analysis. The meta-analysis results showed that the expression of Notch1, Notch3 and NICD was significantly higher in HNSCC as compared with control tissue. There was no significant difference in Jagged1 and HES1 expression between HNSCC and control tissue. Stratified analysis results showed that the expression of Notch1 was significantly higher in poor differentiation, III and IV stage and positive lymph node metastasis patients. Additionally, over-expression of Notch1, NICD, HES1 and DLL4 significantly predicted poor OS in HNSCC patients.. The Notch signaling pathway plays an important role in tumor development of HNSCC. Inhibition of the Notch signaling pathway is a potential therapeutic method of HNSCC.

Topics: Adaptor Proteins, Signal Transducing; Calcium-Binding Proteins; Carcinoma, Squamous Cell; Cell Differentiation; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Neoplasm Staging; Odds Ratio; Receptor, Notch1; Receptors, Notch; Risk Factors; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Survival Analysis; Time Factors; Transcription Factor HES-1

The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.. Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.. Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P < 0.001) and p21 (P = 0.03) expression, but not with Cyclin D1. NOTCH1 expression was significantly associated to early stages (I-II), non-recurrent disease, and better disease-specific (DSS) and overall survival (OS) rates (P < 0.001). Moreover, triple-positive cases (NOTCH1+/HES1+/p21+) exhibited significantly improved DSS (P < 0.001) and OS (P = 0.004), thus reinforcing the association of NOTCH pathway activation with a better prognosis in HNSCC. Multivariate analysis further revealed membranous NOTCH1 expression as a robust independent predictor of better DSS (HR = 0.554; 95% IC 0.412-0.745; P < 0.001) and better OS (HR = 0.640; 95% CI 0.491-0.835; P = 0.001).. These findings show the association of NOTCH pathway activation with a better prognosis in HNSCC patients, also revealing membranous NOTCH1 expression as a robust independent predictor of improved survival. Accordingly, these results suggest a tumor suppressive rather than an oncogenic role for NOTCH pathway in HNSCC.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Line, Tumor; Computational Biology; Disease Management; Disease Susceptibility; Female; Gene Expression; Gene Expression Profiling; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Proportional Hazards Models; Receptors, Notch; Recurrence; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Transcription Factor HES-1