Dysregulation of Redox Status in Urinary Bladder Cancer Patients

The alteration of redox homeostasis constitutes an important etiological feature of common human malignancies. We investigated DNA damage, selenium (Se) levels and the expression of cytoprotective genes involved in (1) the KEAP1/NRF2/ARE pathway, (2) selenoprotein synthesis, and (3) DNA methylation and histone deacetylation as putative key players in redox status dysregulation in the blood of urinary bladder cancer (UBC) patients. The study involved 122 patients and 115 control individuals. The majority of patients presented Ta and T1 stages. UBC recurrence occurred within 0.13 to 29.02 months. DNA damage and oxidative DNA damage were significantly higher in the patients compared to the controls, while plasma Se levels were significantly reduced in the cases compared to the controls. Of the 25 investigated genes, elevated expression in the peripheral blood leukocytes in patients was observed for NRF2, GCLC, MMP9 and SEP15, while down-regulation was found for KEAP1, GSR, HMOX1, NQO1, OGG1, SEPW1, DNMT1, DNMT3A and SIRT1. After Bonferroni correction, an association was found with KEAP1, OGG1, SEPW1 and DNMT1. Early recurrence was associated with the down-regulation of PRDX1 and SRXN1 at the time of diagnosis. Peripheral redox status is significantly dysregulated in the blood of UBC patients. DNA strand breaks and PRDX1 and SRXN1 expression may provide significant predictors of UBC recurrence.