High-throughput metabolomics to identify metabolites to serve as diagnostic biomarkers of prostate cancer

Abstract

Prostate cancer (PCa) has long been known to exhibit unique metabolite profiles. Advances in liquid chromatography mass spectrometry technology have led to the application of metabolomic profiling to PCa toward identifying metabolic alterations in PCa that may provide clinically useful biomarkers. In this work, a metabolomics platform comprised of fast ultrahigh performance liquid chromatography-tandem mass spectrometry (FPLC/MS) coupled with multivariate statistical analyses was employed to identify the serum biomarker(s) associated with the entire measurable metabolome from PCa patients and age-matched healthy controls. Metabolic differences among PCa and control subjects were identified based on orthogonal signal correction-partial least squares discriminant analysis. 2-Isopropyl citrate, cytidine, D-asparagine, N-acetylgalactosamine-4-sulphate, 5-hydroxy-N-formylkynurenine and D-4-O-methyl-myo-inositol in the PCa subjects were significantly different from the control cases. To demonstrate the utility of serum biomarkers for the early diagnosis of PCa, three metabolites comprising 2-isopropyl citrate, cytidine and D-asparagine were selected as candidate biomarkers (AUC > 0.95) and validation in independent patient cohorts yielded satisfactory sensitivity. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Potentially, the present study provides the diagnosis tool for PCa in its early stage.