Abstract

Simple SummaryBladder cancer is one of the most frequently diagnosed cancers worldwide and due to non-specific symptoms, it is often detected at a late stage. For this reason, possible diagnostic alternatives that could be used for non-invasive screening are still being sought. In recent years, metabolomics approach has been frequently used for this type of research, using urine or blood collected from two groups: patients with a given disease and healthy volunteers. Usually, to minimize the impact of between-subject differences, participants of the study are matched in terms of age, gender, or BMI. Another way to rule out the impact of this variability is to analyze samples taken at intervals from the same patient. Therefore, the aim of our study was to validate results obtained using the traditional approach on a small group of patients, from whom samples were taken before and after resection of the bladder tumor, in a given time frame.The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer.

Highlights

  • Age-standardized incidence rates (ASR) of bladder cancer (BCa) increased from 5.3 per100,000 in 2012 to 5.6 per 100,000 in 2020 [1,2]

  • All the subjects participating in the study were patients at the Urology Clinic of the Medical University of Gdansk diagnosed with non-muscle-invasive bladder cancer (NMIBC)

  • It was observed that the levels of some metabolites determined the day after transurethral resection of bladder tumor (TURBT) clearly differed both from the state before surgery and two weeks after TURBT

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Summary

Introduction

Age-standardized incidence rates (ASR) of bladder cancer (BCa) increased from 5.3 per100,000 in 2012 to 5.6 per 100,000 in 2020 [1,2]. Age-standardized incidence rates (ASR) of bladder cancer (BCa) increased from 5.3 per. Statistics show that the presence of at least one BCa risk factor increases the risk of developing the disease even several times. The risk of developing the disease is more than four times higher in men than in women, and the proportion is similar in terms of mortality (3.2/100,000 in men and 0.9/100,000 in women). The most important known BCa risk factor, increases the chance of developing the disease by about four times. It has been shown that cigarette smoking reduces the chances of recovery when cancer relapses and increases the risk of developing an invasive stage of the disease [2,3]

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