Elevated urinary total sialic acid and increased oxidative stress in patients with bladder cancer

Abstract

Background:Increased production and release of sialic acid have been reported in many malignant conditions including bladder cancer. 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) have been widely used as oxidative stress biomarkers. Objective: Determine urinary levels of total sialic acid (TSA), 8-OHdG, and MDA in patients with urinary bladder cancer, and evaluate their clinical relevance. Patients and methods: Forty-five patients with histologically proven bladder cancer and 41 healthy subjects were recruited for the study. Morning urine samples were collected from all participants for measurements of TSA, 8-OHdG and MDA using thiobarbituric assay, competitive ELISA and spectrophotometry methods, respectively. Histological examination was performed for all patients. Results: Bladder cancer patients excreted urinary TSA, 8-OHdG, and MDA significantly higher than healthy controls. Based on receiver operating characteristic curve analysis, urinary TSA had adequate diagnostic potential to distinguish patients from healthy populations, and its cutoff value was chosen at 95.26 μg/g creatinine. Sensitivity, specificity, and accuracy of urinary TSA determination were 75.6%, 75.6%, and 75.6%, respectively. Both in patient and healthy groups, urinary TSA was linearly correlated with urinary 8-OHdG. Patients with highseverity grade (n=27) excreted urinary TSA significantly greater than those with low-severity grade (n=18). Conclusion: Urinary TSA, 8-OHdG, and MDA increased in patients with bladder cancer. The elevated urinary TSA was associated with enhanced oxidative stress. In addition, urinary TSA increased with progressiveness of the tumor.

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

“…The most common risk factors for bladder cancer are cigarette smoking, exposure to industrial carcinogens (aromatic amines), high levels of arsenic intake and diet [150]. Oxidative stress critically contributes to the development of bladder cancer [151]. Various lines of evidence reported an increased oxidative stress in patients with breast cancer [152,153].…”

“…Oxidative stress critically contributes to the development of bladder cancer [151]. Various lines of evidence reported an increased oxidative stress in patients with breast cancer [152,153]. Increased NO levels have been reported in bladder cancer patients [154].…”

LINE‐1 hypomethylation induced by reactive oxygen species is mediated via depletion of S‐adenosylmethionine

“…Recently, we demonstrated hypomethylation of LINE‐1 in peripheral blood and urinary exfoliated cells obtained from patients with bladder cancer . These patients also had increased levels of oxidative stress . Interestingly, a significant correlation between increased oxidative stress and decreased LINE‐1 methylation was observed, not only in bladder cancer patients but also in healthy subjects .…”

“…9 These patients also had increased levels of oxidative stress. 9,10 Interestingly, a significant correlation between increased oxidative stress and decreased LINE-1 methylation was observed, not only in bladder cancer patients but also in healthy subjects. 9 This suggests that oxidative stress (not cancer per se) is fundamentally associated with LINE-1 hypomethylation.…”

Oxidative Stress Induces Hypomethylation of LINE-1 and Hypermethylation of the RUNX3 Promoter in a Bladder Cancer Cell Line

“…Beside genetic mutations and epigenetic alterations, oxidative stress is also critically involved in the bladder cancer carcinogenesis. Increase in oxidative stress in patients with bladder cancer has been reported (Akcay et al, 2003, Opanuraks et al, 2010. Reactive oxygen species (ROS) directly damage the cellular DNA and promote tumor development not only through genetic mutations, but also through epigenetic alterations (Wachsman, 1997).…”