Dataset Information

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers.

ABSTRACT: INTRODUCTION:To date, no reliable prognostic biological marker for all squamous cell carcinoma located in different subsites of the head and neck region has been identified and used in daily routine. In line with our previous studies, in which we showed a role of glutathione and associated enzymes as potential biological markers, we investigated the relationship between GPx1 and prognosis of head and neck squamous cell carcinoma. METHODS:The association between GPx1 and patient and tumor related factors were investigated in 87 pretreatment biopsies from head and neck cancer patients treated by (chemo)radiation. Moreover, the influence of GPx1 expression on outcome parameters was assessed. RESULTS:A significant difference was found in the T-stage between the low and high-expressing GPx1 groups. About 75% of the T3-T4 tumors were considered GPx1 low-expressing tumors, while low GPx1 expression was only seen in 25% of the T1-T2 tumors. There was also a significant difference found between the groups when looking at the different tumor sites. Local control, locoregional control, disease-free survival, and overall survival were the same in both groups. All these results indicate that GPx1 expression does not influence the radiotherapy response nor survival.

SUBMITTER: Dequanter D

PROVIDER: S-EPMC5423422 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers.

Dequanter Didier D Dok Ruveyda R Koolen Louet L Vander Poorten Vincent V Nuyts Sandra S

Frontiers in oncology 20170509

<h4>Introduction</h4>To date, no reliable prognostic biological marker for all squamous cell carcinoma located in different subsites of the head and neck region has been identified and used in daily routine. In line with our previous studies, in which we showed a role of glutathione and associated enzymes as potential biological markers, we investigated the relationship between GPx1 and prognosis of head and neck squamous cell carcinoma.<h4>Methods</h4>The association between GPx1 and patient an ...[more]

PMID: 28536671

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Project description:BackgroundGlutathione peroxidase-1 (GPX1) is generally expressed in tissues with high oxygen tension such as the kidneys and lungs, and its main function is to degrade reactive oxygen species (ROS) and protect cells from oxidative stress. Studies have shown that GPX1 is upregulated in many tumor tissues and is closely related to tumor progression and metastasis. This study aimed to explore the possibility of GPX1 as a biomarker for kidney chromophobe cell carcinoma (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC).MethodsThe Oncomine and GEPIA databases were used to analyze the GPX1 expression differences between tumor and normal tissues, and the UALCAN, GEPIA and DriverDBv3 databases were used to perform the survival analyses. The GeneMANIA interactive tool was then used to find the GPX1-related protein-protein interaction (PPI). Following this, the LinkedOmics database was used for the enrichment analysis of GPX1, and the Timer database was used to estimate the abundance of immune infiltration. Finally, quantitative polymerase chain reaction (qPCR) was performed on patient specimens collected in the clinic to confirm the database findings.ResultsIn our study, we found that the expression of GPX1 in three types of renal cell carcinoma (RCC) were upregulated, and the high expression of GXP1 was related to the poor prognosis of patients with KICH and KIRC. On the contrary, KIRP patients with a high expression of GPX1 had a better prognosis. In addition, GPX1 was related to the abundance of immune cell infiltration. The results of the qPCR analysis confirmed that the expression of GPX1 in RCC was increased compared with the control group (P<0.05).ConclusionsOur results indicate that the expression of GPX1 is related to the prognosis of three types of RCC. As such, GPX1 expression could be a reliable diagnostic and prognostic biomarker for RCC and, more importantly, may provide a new direction for therapeutic strategies.

Project description:BackgroundSince targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.MethodsWe conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.ResultsBreast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).ConclusionsGPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

Dataset Information

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers.

Publications

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers.

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