Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Abstract

Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography–mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa.

Metabolic signature of extracellular vesicles depends on the cell culture conditions

“…Although the EV‐metabolome is still largely unknown, it shows great promise to be mined for information such as biomarkers of systematic diseases, e.g. cancer, as already suggested by the few pioneering studies [58–61].…”

Identification of Plasma Glycosphingolipids as Potential Biomarkers for Prostate Cancer (PCa) Status

“…Two recent systematic reviews of metabolomics biomarkers in PCa identified very few studies where sphingolipids were observed in their analyses [ 12 , 13 ]. Studies by Clos-Garcia et al demonstrated decreased levels of ceramides (d18:1/16:0, d18:1/20:0, and d18:1/22:0) in urine extracellular vesicles from stage 3 PCa patients as compared to patients with stage 2 disease [ 31 ]. Metabolic fingerprinting of urine from PCa patients and healthy volunteers demonstrated increased sphingosine levels in PCa patients [ 32 ].…”

Metabolic characteristics of large and small extracellular vesicles from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy

“…EVs have important roles in regulating cellular communication, growth, migration, angiogenesis and immune modulation [13,14]. Numerous studies have revealed that EVs in bodily fluids, such as the blood, urine, and cerebrospinal fluid can be used as promising biomarkers to avoid repeated biopsies, particularly for cancer diagnosis [15,16]. Samples of pleural effusion have been widely used for screening to identify biomarkers of tuberculosis and lung cancer, given its anatomical proximity to the lung and key part role in the immune microenvironment in the chest [17,18].…”