Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer.
Adult
Aged
Aged, 80 and over
Colorectal Neoplasms
/ metabolism
Disease-Free Survival
Female
Hedgehog Proteins
/ metabolism
Humans
Jagged-1 Protein
/ metabolism
Kaplan-Meier Estimate
Male
Middle Aged
Prognosis
Receptor, Notch2
/ metabolism
Receptor, Notch3
/ metabolism
Signal Transduction
Young Adult
Gli-1
Hedgehog
Jagged-1
Notch
Notch-2
Notch-3
Patched-1
Shh
Smo
colorectal cancer
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
14
02
2019
revised:
06
03
2019
accepted:
14
03
2019
entrez:
7
4
2019
pubmed:
7
4
2019
medline:
16
4
2019
Statut:
ppublish
Résumé
Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes. Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis. Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident. Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes.
MATERIALS AND METHODS
METHODS
Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis.
RESULTS
RESULTS
Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident.
CONCLUSION
CONCLUSIONS
Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.
Identifiants
pubmed: 30952759
pii: 39/4/2129
doi: 10.21873/anticanres.13326
doi:
Substances chimiques
Hedgehog Proteins
0
JAG1 protein, human
0
Jagged-1 Protein
0
NOTCH2 protein, human
0
NOTCH3 protein, human
0
Receptor, Notch2
0
Receptor, Notch3
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2129-2138Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.