Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma.
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Line, Tumor
Computational Biology
/ methods
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
/ genetics
Recurrence
Signal Transduction
Squamous Cell Carcinoma of Head and Neck
/ diagnosis
Transcription Factor HES-1
/ genetics
HES1
Head and neck squamous cell carcinoma
NOTCH1
Prognosis
Survival
Journal
Oral oncology
ISSN: 1879-0593
Titre abrégé: Oral Oncol
Pays: England
ID NLM: 9709118
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
20
08
2020
accepted:
04
09
2020
pubmed:
16
9
2020
medline:
10
7
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32932170
pii: S1368-8375(20)30439-5
doi: 10.1016/j.oraloncology.2020.105003
pii:
doi:
Substances chimiques
Receptors, Notch
0
Transcription Factor HES-1
0
HES1 protein, human
149348-15-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105003Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.