Abstract
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.
Highlights
Cancer incidence and cancer deaths comprise one of the major public health problems in the world.Urinary bladder cancer (UBC) incidence, diagnosed in both sexes combined, ranks 10th place with549,393 estimated new cases in 2018
We focused on the effects of oxidative stress formation in the blood of urinary bladder cancer (UBC) patients, measured by molecular markers in peripheral blood leukocytes, genomic instability via a comet assay in peripheral lymphocytes and Se levels in the plasma
Recurrence occurred in patients (≤1 year after the diagnosis and/or transurethral resection of bladder tumor (TURBT)), and late recurrence was observed in patients, while 22 patients were free from disease recurrence
Summary
Cancer incidence and cancer deaths comprise one of the major public health problems in the world.Urinary bladder cancer (UBC) incidence, diagnosed in both sexes combined, ranks 10th place with549,393 estimated new cases in 2018. Cancer incidence and cancer deaths comprise one of the major public health problems in the world. Urinary bladder cancer (UBC) incidence, diagnosed in both sexes combined, ranks 10th place with. UBC is more common in men than in women and ranks fourth place among cancers in men in Poland, with 8197 cases (8.6% of new cases in 2018) The majority (90–95%) of UBCs—transitional cell carcinomas—comprise superficial tumors (70%), which are usually low-grade and non-invasive (non-muscle invasive bladder cancer, NMIBC) with stage Ta/T1, and the second type has a form of muscle-invasive disease (MIBC), Cancers 2020, 12, 1296; doi:10.3390/cancers12051296 www.mdpi.com/journal/cancers. The overall rate of recurrence for NMIBC is 60% to 70% and the overall rate of progression to a higher stage or grade, and metastasis is 20% to 30% [2]
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