Abstract

The aim of this pilot study is to evaluate sarcosine, uracil, and kynurenic acid in urine as potential biomarkers in prostate cancer detection and progression monitoring. Sarcosine, uracil, and kynurenic acid were measured in urine samples of 32 prostate cancer patients prior to radical prostatectomy, 101 patients with increased prostate-specific antigen prior to ultrasonographically-guided prostatic biopsy collected before and after prostatic massage, and 15 healthy volunteers (controls). The results were related to histopathologic data, Gleason score, and PSA (Prostate Specific Antigen). Metabolites were measured after analysis of urine samples with Ultra-High Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) instrumentation. Multivariate, nonparametric statistical tests including receiver operating characteristics analyses, one-way analysis of variance (Kruskal–Wallis test), parametric statistical analysis, and Pearson correlation, were performed to evaluate diagnostic performance. Decreased median sarcosine and kynurenic acid and increased uracil concentrations were observed for patients with prostate cancer compared to participants without malignancy. Results showed that there was no correlation between the concentration of the studied metabolites and the cancer grade (Gleason score <7 vs. ≥7) and the age of the patients. Evaluation of biomarkers by ROC (Receiving Operating Characteristics) curve analysis showed that differentiation of prostate cancer patients from participants without malignancy was not enhanced by sarcosine or uracil levels in urine. In contrast to total PSA values, kynurenic acid was found a promising biomarker for the detection of prostate cancer particularly in cases where collection of urine samples was performed after prostatic massage. Sarcosine and uracil in urine samples of patients with prostate cancer were not found as significant biomarkers for the diagnosis of prostate cancer. None of the three metabolites can be used reliably for monitoring the progress of the disease.

Highlights

  • Identification and quantification of numerous endogenous metabolites in various complex biological samples became possible due to recent advances in mass spectrometry-related technologies

  • There were no statistical significant observations, in general sarcosine presented at higher concentration levels in case of inflammation for both pre- and post-prostatic massage (PM) categories and uracil levels were found increased in participants with normal results after Urine samples were collected preoperatively; group B (UGPB) only in samples that collected after PM

  • The present pilot study is an attempt is an attempt to investigate whether sarcosine in urine is a suitable alternative biomarker for prostate cancer (PCa) to investigate whether sarcosine in urine is a suitable alternative biomarker for PCa detection and detection and progression monitoring [5,12]

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Summary

Introduction

Identification and quantification of numerous endogenous metabolites in various complex biological samples became possible due to recent advances in mass spectrometry-related technologies. Results of such analysis may provide a better understanding of alterations in molecular pathways of patients including those with cancer [1,2]. The aim of this study is to assess the potential of urinary metabolites sarcosine, uracil, and kynurenic acid as biomarkers for early diagnosis of PCa in three distinct individual categories and for prognosis of the progression and aggressiveness of the tumor. In order to study the above urine samples of individuals with radical prostatectomy, Ultrasonographically-Guided Prostatic Biopsy and controls were analyzed by a UPLC-MS/MS method able to detect and quantify the metabolites of interest including sarcosine, kynurenic acid and uracil. Multivariate and univariate analysis were further performed in order to find any correlation of the studied metabolites with the prognosis and the progression monitoring of prostate cancer

Characteristics of Study Population
Results
Histopathologic Results p
Histopathologic Results
Participants with PCa undergoing
Discussion
Reagents and Materials
Samples and Sample Preparation
Statistical Analysis
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