Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery

Sensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible liquid biopsies. Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in PCa patients and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. The mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supports a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in prostate cancer, which can be exploited for novel biomarkers and therapies.