TY  - JOUR
AU  - Kreycy, Nele
AU  - Gotzian, Christiane
AU  - Fleming, Thomas
AU  - Flechtenmacher, Christa
AU  - Grabe, Niels
AU  - Plinkert, Peter
AU  - Hess, Jochen
AU  - Zaoui, Karim
TI  - Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.
JO  - BMC cancer
VL  - 17
IS  - 1
SN  - 1471-2407
CY  - London
PB  - BioMed Central
M1  - DKFZ-2017-01185
SP  - 382
PY  - 2017
AB  - 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.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.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.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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28549423
C2  - pmc:PMC5446730
DO  - DOI:10.1186/s12885-017-3367-5
UR  - https://inrepo02.dkfz.de/record/124289
ER  -