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Glutathione peroxidase 4 (GPX4) protects cells against peroxides, and is a novel tumor suppressor gene. We hypothesize that GPX4 expression is lost in bladder urothelial carcinoma (BUC) and a decrease in GPX4 expression in cancer cells is associated with a poor prognosis for BUC. We conducted a retrospective study of BUC to evaluate the expression pattern of GPX4 mRNA and protein, and its relevance to the pathologic features and survival. Immunohistochemistry for GPX4 was performed on tissue microarrays of BUC from 89 patients, which was followed by analysis of GPX4 expression in these tumor tissues using real time PCR and western blotting. We conducted a retrospective study of 109 BUC patients followed at the University of Washington and evaluated the relationships among GPX4 expression and patient clinicopathological factors and survival. We found that GPX4 expression was maintained in normal urothelial cells, but was often downregulated in BUC (P < 0.001). By contrast, the GPX4 mRNA level was significantly lower in carcinoma cells compared to normal urothelium (P < 0.001). However, there was no difference in protein levels of GPX4 between tumor cells and normal urothelium. Univariate analysis revealed that reduced tumor expression of GPX
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