Introduction: Prostate cancer (PCa) pathogenesis is influenced by alterations in cellular metabolism. Metabolomics measures these biochemical changes to create global tissue metabolite profiles. Urinary studies are noninvasive and can potentially identify biomarkers for PCa. We used Capillary Electrophoresis Mass Spectrometry (CE-MS) to analyze urine from men undergoing prostate biopsy to investigate their metabolomic profiles.
Methods: An analysis of charged metabolites by CE-MS was performed as described (J Proteome Res. 2:488; 2003) on 40 urine specimens (20 men with PCa, 20 men without PCa). Urinary metabolites were extracted from 100 µL urine and mixed with methanol containing 20 µM of internal standards. CE-MS experiments were performed with the Agilent CE system. Screening of potential biomarkers was performed with statistical protocols and pathway analyses. Metabolites with levels below the detection limit in all samples were excluded. Relative abundances of metabolites were normalized to levels of creatinine.
Results: CE-MS analysis produced thousands of features in the anionic and cationic modes. A volcano plot comparing p values against fold change identified 60 metabolites that were statistically different between urine samples of men with PCa and those of men without PCa. Pathway analysis using MetaboAnalyst (Metabolites 9:57; 2019) showed high activity in ceramide, short chain fatty acid (SCFA), branched chain amino acid, serine, threonine and tryptophan metabolism. Figure 1: Pathway analysis, fold change represented by color and vertical scale, number of significant metabolites by size. Figure 2 graphically contrasts metabolomic profiles.
Conclusions: CE-MS analysis identified several metabolic pathways that were up-regulated in urine of men with PCa. These metabolites are involved in steroid, aromatic, microorganism and SCFA processes and warrant targeted studies, which are underway in our lab. If validated, they have potential to serve as non-invasive biomarkers for PCa diagnosis and therapeutics. Source of
