Dysregulation of Redox Status in Urinary Bladder Cancer Patients

Area of Science:

• Biochemistry and Molecular Biology
• Oncology
• Genetics

Background:

• Redox homeostasis alteration is a key factor in human malignancies, including urinary bladder cancer (UBC).
• Investigating the KEAP1/NRF2/ARE pathway, selenoprotein synthesis, and DNA methylation/histone deacetylation offers insights into redox dysregulation in UBC.

Purpose of the Study:

• To investigate DNA damage, selenium levels, and the expression of specific cytoprotective genes in blood of UBC patients.
• To identify potential key players in redox status dysregulation and their association with UBC and recurrence.

Main Methods:

• Analysis of DNA damage, plasma selenium levels, and gene expression in peripheral blood leukocytes from 122 UBC patients and 115 controls.
• Focus on genes involved in the KEAP1/NRF2/ARE pathway, selenoprotein synthesis, and DNA methylation/histone deacetylation.
• Statistical analysis including Bonferroni correction to identify significant associations and predictors of early recurrence.

Main Results:

• UBC patients exhibited significantly higher DNA damage and lower plasma selenium levels compared to controls.
• Elevated expression of NRF2, GCLC, MMP9, and SEP15, and down-regulation of KEAP1, GSR, HMOX1, NQO1, OGG1, SEPW1, DNMT1, DNMT3A, and SIRT1 were observed in patients.
• Down-regulation of PRDX1 and SRXN1 was associated with early UBC recurrence.

Conclusions:

• Peripheral redox status is significantly dysregulated in UBC patients.
• Specific gene expression patterns and DNA damage levels are associated with UBC.
• DNA strand breaks and PRDX1/SRXN1 expression may serve as significant predictors for UBC recurrence.