Seminal plasma enables selection and monitoring of active surveillance candidates using nuclear magnetic resonance-based metabolomics: A preliminary investigation

Abstract

BackgroundDiagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort.Materials and methodsSeminal plasma samples of 151 men being investigated for prostate cancer were analyzed with 1H-NMR spectroscopy. After adjustment for buffer (add-to-subtract) and endogenous enzyme influence on metabolites, metabolite profiling was performed with multivariate statistical analysis (principal components analysis, partial least squares) and targeted quantitation.ResultsSeminal plasma metabolites best predicted low- and intermediate-risk prostate cancer with differences observed between these groups and benign samples. Lipids/lipoproteins dominated spectra of high grade samples with less metabolite contributions. Overall prostate cancer prediction using previously described metabolites was not validated.ConclusionMetabolomics of seminal plasma in vitro may assist urologists with diagnosis and monitoring of either low or intermediate grade prostate cancer. Less clinical benefit may be observed for high-risk patients. Further investigation in active surveillance cohorts, and/or in combination with in vivo magnetic resonance spectroscopic imaging may further optimize localized prostate cancer outcomes.

NMR‐based metabolomics of biofluids in cancer

“…Several studies on small cohorts have searched for PCa biomarkers in semen or expressed prostatic secretions, showing decreased citrate levels in PCa compared with healthy controls . This could however not be confirmed in a larger study performing metabolic profiling of seminal plasma from 151 high‐risk participants, of which 98 had proven PCa . In this cohort, citrate was not a predictor for PCa, and the significant metabolites choline and leucine did not improve diagnosis compared with PSA measurements.…”

Metabolomics Biomarkers of Prostate Cancer: A Systematic Review

“…Roberts et al conducted a study using seminal plasma for selection and monitoring of active surveillance candidates using NMR based metabolomics [63]. One hundred fifty-one men who were investigated for elevated PSA and/or abnormal DRE were included in the prospective cohort study.…”

Metabolomics Contributions to the Discovery of Prostate Cancer Biomarkers

“…PCa is a disease of great interest from a metabolomics perspective. A number of studies, focused on the characterization of the specific PCa metabolic phenotype using different experimental approaches, have been reported recently [37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61]. These studies have shown that healthy prostate cells are characterized by a decreased citrate oxidation and metabolism within the tricarboxylic acid (TCA) cycle, resulting in citrate accumulation [62] and the reliance on glucose oxidation for energy production [63].…”

“…This study revealed that concentrations of citrate, myo-inositol, and spermine were inversely correlated with PCa risk (AUC values of 0.89, 0.87 and 0.79, respectively). However, in a more recent study attempting to validate the role of these metabolites as biomarkers for assessing PCa risk, Roberts et al found that citrate, spermine, and myo-inositol had minimal predictive ability when analyzing seminal fluid samples [61]. Therefore, further studies using larger cohorts will be required to confirm the utility of seminal fluid and EPS derived biomarkers for PCa diagnosis and prognosis.…”