A novel expressed prostatic secretion(EPS)-urine metabolomic signature for the diagnosis of clinically significant prostate cancer

摘要

Objective:Significant efforts are currently being made to identify novel biomarkers for the diagnosis and risk stratification of prostate cancer(PCa).Metabolomics can be a very useful approach in biomarker discovery because metabolites are an important read-out of the disease when characterized in biological samples.We aimed to determine a metabolomic signature which can accurately distinguish men with clinically significant PCa from those affected by benign prostatic hyperplasia(BPH).Methods:We first performed untargeted metabolomics using ultrahigh-performance liquid chromatography tandem mass spectrometry on expressed prostatic secretion urine(EPS-urine)from 25 patients affected by BPH and 25 men with clinically significant PCa(defined as Gleason score≥3+4).Diagnosis was histologically confirmed after surgical treatment.The EPS-urine metabolomic approach was then applied to a larger,prospective cohort of 92 consecutive patients undergoing multiparametric magnetic resonance imaging for clinical suspicion of PCa prior to biopsy.Results:We established a novel metabolomic signature capable of accurately distinguishing PCa from benign tissue.A metabolomic signature was associated with clinically significant PCa in all subgroups of the Prostate Imaging Reporting and Data System(PI-RADS)classification(100%and 89.13%of accuracy when the PI-RADS was in range of 1–2 and 4–5,respectively,and 87.50%in the more critical cases when the PI-RADS was 3).Conclusions:A combination of metabolites and clinical variables can effectively help in identifying PCa patients that might be overlooked by current imaging technologies.Metabolites from EPS-urine should help in defining the diagnostic pathway of PCa,thus improving PCa detection and decreasing the number of unnecessary prostate biopsies.