1H NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer

Background: Prostate cancer (PCa) is a common health problem worldwide. The rate of this disease is likely to grow by 2021. PCa is a heterogeneous disorder, and various biochemical factors contribute to the development of this disease. The metabolome is the complete set of metabolites in a cell or biological sample and represents the downstream end product of the omics. Hence, to model PCa by computational systems biology, a preliminary metabolomics-based study was used to compare the metabolome profile pattern between healthy and PCa men. Objective: This study was carried out to highlight energy metabolism modification and assist the prognosis and treatment of disease with unique biomarkers. Materials and Methods: In this cross-sectional research, 26 men diagnosed with stage-III PCa and 26 healthy men with normal PSA levels were enrolled. Urine was analyzed with proton nuclear magnetic resonance (1H-NMR) spectroscopy, accompanied by the MetaboAnalyst web-based platform tool for metabolomics data analysis. Partial least squares regression discriminant analysis was applied to clarify the separation between the two groups. Outliers were documented and metabolites determined, followed by identifying biochemical pathways. Results: Our findings reveal that modifications in aromatic amino acid metabolism and some of their metabolites have a high potential for use as urinary PCa biomarkers. Tryptophan metabolism (p < 0.001), tyrosine metabolism (p < 0.001), phenylalanine, tyrosine and tryptophan biosynthesis (p < 0.001), phenylalanine metabolism (p = 0.01), ubiquinone and other terpenoid-quinone biosynthesis (p = 0.19), nitrogen metabolism (p = 0.21), and thiamine metabolism (p = 0.41) with Q2 (0.198) and R2 (0.583) were significantly altered. Conclusion: The discriminated metabolites and their pathways play an essential role in PCa causes and harmony. Key words: Metabolomics, Prostate cancer, Aromatic amino acids, 1H-NMR spectroscopy.

Download Full-text

215: Analysis of Citrate in Human Seminal Fluid by 1H NMR Spectroscopy Distinguishes Prostate Cancer From Normal/Bph

The Journal of Urology ◽

10.1016/s0022-5347(18)34480-x ◽

2005 ◽

Vol 173 (4S) ◽

pp. 59-59

Author(s):

Eric E. Kline ◽

Tiffany A. Averna ◽

Anthony Y. Smith ◽

Laurel O. Sillerud

Keyword(s):

Prostate Cancer ◽

Nmr Spectroscopy ◽

1H Nmr ◽

1H Nmr Spectroscopy ◽

Seminal Fluid

Download Full-text

Nuclear magnetic resonance spectroscopy of expressed prostatic secretions: Metabolite citrate and derivatives are potential markers of prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4623 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4623-4623

Author(s):

D. Crawford ◽

N. Serkova ◽

E. Gamito ◽

R. Jones ◽

C. O’Donnell ◽

...

Keyword(s):

Prostate Cancer ◽

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Nuclear Magnetic Resonance Spectroscopy ◽

1H Nmr ◽

Resonance Spectroscopy ◽

Absolute Concentration ◽

Absolute Concentrations ◽

Nuclear Magnetic

4623 Background: Nuclear magnetic resonance spectroscopy (NMRS) along with a novel method for determining absolute concentrations of metabolites were utilized to analyze expressed prostatic secretions (EPS) from men with prostate cancer (PCa) and from healthy controls. Methods: Flash frozen EPS samples from 66 men (40 with PCa and 26 controls) were analyzed by high-resolution 1H-NMR spectroscopy using a Bruker 500 MHz DRX NMR spectrometer with a 1-mm microprobe. The total number of scans per fully relaxed 1H-NMR spectrum was n = 40 with water suppression. Absolute concentrations of endogenous metabolites (citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamate, acetate, hydroxybutyrate) were quantified using trimethylsilyl-propionic acid as an external standard reference. Stepwise multivariable logistic regression (LR) was used to model the risk of PCa based upon the levels of the measured metabolites. Results: The average age of the EPS donors was 54.7 ± 9.8 years. The median Gleason score for the men with PCa was 6 (range 5–9). The Wilcoxon rank sum test indicated that citrate, spermine, inositol, citrate/spermine, and citrate/lactate were all significant predictors of PCa (p < .001). The LR models indicated that the absolute concentration of citrate was highly predictive of PCa with lower concentrations resulting in a higher risk of cancer. The area under the receiver operating characteristic curve (AUROC) for citrate alone was 0.79 (95% CI 0.75–0.83). Using relative concentrations (metabolite ratios) in a two-variable LR model, citrate/spermine and citrate/lactate were also predictive of PCa with an AUROC of 0.76 (95% CI 0.71–0.81). Conclusions: The results suggest that absolute concentration of citrate and its derivatives in EPS as measured by NMRS have promising potential as accurate markers of prostate cancer. No significant financial relationships to disclose.

Download Full-text

Novel Metabolic Signatures of Prostate Cancer Revealed by 1H-NMR Metabolomics of Urine

Diagnostics ◽

10.3390/diagnostics11020149 ◽

2021 ◽

Vol 11 (2) ◽

pp. 149

Author(s):

Bo Yang ◽

Chuan Zhang ◽

Sheng Cheng ◽

Gonghui Li ◽

Jan Griebel ◽

...

Keyword(s):

Prostate Cancer ◽

1H Nmr ◽

Gleason Score ◽

Wilcoxon Test ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Potential Candidate ◽

Differential Analysis ◽

Operating Characteristics ◽

Novel Biomarkers

Prostate cancer (PC) is one of the most common male cancers worldwide. Until now, there is no consensus about using urinary metabolomic profiling as novel biomarkers to identify PC. In this study, urine samples from 50 PC patients and 50 non-cancerous individuals (control group) were collected. Based on 1H nuclear magnetic resonance (1H-NMR) analysis, 20 metabolites were identified. Subsequently, principal component analysis (PCA), partial least squares-differential analysis (PLS-DA) and ortho-PLS-DA (OPLS-DA) were applied to find metabolites to distinguish PC from the control group. Furthermore, Wilcoxon test was used to find significant differences between the two groups in metabolite urine levels. Guanidinoacetate, phenylacetylglycine, and glycine were significantly increased in PC, while L-lactate and L-alanine were significantly decreased. The receiver operating characteristics (ROC) analysis revealed that the combination of guanidinoacetate, phenylacetylglycine, and glycine was able to accurately differentiate 77% of the PC patients with sensitivity = 80% and a specificity = 64%. In addition, those three metabolites showed significant differences in patients stratified for Gleason score 6 and Gleason score ≥7, indicating potential use to detect significant prostate cancer. Pathway enrichment analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) and the SMPDB (The Small Molecule Pathway Database) revealed potential involvement of KEGG “Glycine, Serine, and Threonine metabolism” in PC. The present study highlights that guanidinoacetate, phenylacetylglycine, and glycine are potential candidate biomarkers of PC. To the best knowledge of the authors, this is the first study identifying guanidinoacetate, and phenylacetylglycine as potential novel biomarkers in PC.

Download Full-text