Dataset Information

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.

ABSTRACT:

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.

SUBMITTER: Kreycy N

PROVIDER: S-EPMC5446730 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.

Kreycy Nele N Gotzian Christiane C Fleming Thomas T Flechtenmacher Christa C Grabe Niels N Plinkert Peter P Hess Jochen J Zaoui Karim K

BMC cancer 20170526 1

<h4>Background</h4>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.<h4>Methods</h4>Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed ...[more]

PMID: 28549423

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Project description:BACKGROUND:A subset of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) experience poor clinical outcomes. The authors of this report explored prognostic risk factors for overall survival (OS) and recurrence-free survival (RFS). METHODS:Patients with incident HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing as well as demographic and clinicopathologic information (N?=?176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and clinicopathologic information was extracted from medical records. RESULTS:In total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV-OSCC). In the patients with HPV-OSCC, the 3-year and 5-year OS rates were 93% (95% confidence interval [CI], 88%-98%) and 89% (95% CI, 81%-97%), respectively. Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per 10-year increase; 95% CI, 1.05-5.16 per 10-year increase; P?=?.038), patients with advanced clinical T classification (HR, 5.78; 95% CI, 1.60-20.8; P?= .007), and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07-18.0; P?= .04). Disease recurrence was associated with advanced clinical T-classification (HR, 8.32; 95% CI, 3.06-23; P?<?.0001), current/former alcohol use (HR, 13; 95% CI, 1.33-120; P?= .03), and unmarried status (HR, 3.28; 95% CI, 1.20-9.00; P?= .02). Patients who remained recurrence free for 5 years had an 8.6% chance of recurrence by 10 years (1-sided 95% CI upper bound, 19%; P?= .088). CONCLUSIONS:In this study, prognostic risk factors were identified for patients with HPV-OSCC. The observed recurrence rates between 5 years and 10 years after definitive therapy need to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462-3471.. © 2013 American Cancer Society.

Project description:PurposeThere is a lack of biomarkers for accurately prognosticating outcome in both human papillomavirus-related (HPV+) and tobacco- and alcohol-related (HPV-) oropharyngeal squamous cell carcinoma (OPSCC). The aims of this study were to i) develop and evaluate radiomic features within (intratumoral) and around tumor (peritumoral) on CT scans to predict HPV status; ii) investigate the prognostic value of the radiomic features for both HPV- and HPV+ patients, including within individual AJCC eighth edition-defined stage groups; and iii) develop and evaluate a clinicopathologic imaging nomogram involving radiomic, clinical, and pathologic factors for disease-free survival (DFS) prediction for HPV+ patients.Experimental designThis retrospective study included 582 OPSCC patients, of which 462 were obtained from The Cancer Imaging Archive (TCIA) with available tumor segmentation and 120 were from Cleveland Clinic Foundation (CCF, denoted as SCCF) with HPV+ OPSCC. We subdivided the TCIA cohort into training (ST, 180 patients) and validation (SV, 282 patients) based on an approximately 3:5 ratio for HPV status prediction. The top 15 radiomic features that were associated with HPV status were selected by the minimum redundancy-maximum relevance (MRMR) using ST and evaluated on SV. Using 3 of these 15 top HPV status-associated features, we created radiomic risk scores for both HPV+ (RRSHPV+) and HPV- patients (RRSHPV-) through a Cox regression model to predict DFS. RRSHPV+ was further externally validated on SCCF. Nomograms for the HPV+ population (Mp+RRS) were constructed. Both RRSHPV+ and Mp+RRS were used to prognosticate DFS for the AJCC eighth edition-defined stage I, stage II, and stage III patients separately.ResultsRRSHPV+ was prognostic for DFS for i) the whole HPV+ population [hazard ratio (HR) = 1.97, 95% confidence interval (CI): 1.35-2.88, p < 0.001], ii) the AJCC eighth stage I population (HR = 1.99, 95% CI: 1.04-3.83, p = 0.039), and iii) the AJCC eighth stage II population (HR = 3.61, 95% CI: 1.71-7.62, p < 0.001). HPV+ nomogram Mp+RRS (C-index, 0.59; 95% CI: 0.54-0.65) was also prognostic of DFS (HR = 1.86, 95% CI: 1.27-2.71, p = 0.001).ConclusionCT-based radiomic signatures are associated with both HPV status and DFS in OPSCC patients. With additional validation, the radiomic signature and its corresponding nomogram could potentially be used for identifying HPV+ OPSCC patients who might be candidates for therapy deintensification.

Dataset Information

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma.

Similar Datasets

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