title: Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma
creator: Kreycy, Nele
creator: Gotzian, Christiane
creator: Fleming, Thomas
creator: Flechtenmacher, Christa
creator: Grabe, Niels
creator: Plinkert, Peter
creator: Hess, Jochen
creator: Zaoui, Karim
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Background: Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far.   Methods: Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro.   Results: Glyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients.   Conclusions: Induced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.
publisher: BioMed Central; Springer
date: 2017
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/22993/1/12885_2017_Article_3367.pdf
identifier: DOI:10.11588/heidok.00022993
identifier: urn:nbn:de:bsz:16-heidok-229934
identifier:   Kreycy, Nele ; Gotzian, Christiane ; Fleming, Thomas ; Flechtenmacher, Christa ; Grabe, Niels ; Plinkert, Peter ; Hess, Jochen ; Zaoui, Karim  (2017) Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.  BMC Cancer, 17 (382).  pp. 1-9.  ISSN 1471-2407     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/22993/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng