TY - JOUR
T1 - Urinary Extracellular Vesicle Signatures as Biomarkers in Prostate Cancer Patients
AU - Lange, Sigrun
AU - Bernstein, Darryl Ethan
AU - Dimov, Nikolay
AU - Puttaswamy, Srinivasu
AU - Johnston, Ian
AU - Kraev, Igor
AU - Needham, Sarah R.
AU - Vasdev, Nikhil
AU - Inal, Jameel
N1 - © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons
Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
PY - 2025/7/18
Y1 - 2025/7/18
N2 - Urinary extracellular vesicles (U-EVs) are gaining increasing interest as non-invasive liquid biopsy tools for clinical use. Prostate cancer (PCa) is amongst the highest cancer-related causes of death in men, and therefore, the identification of non-invasive, robust biomarkers is of high importance. This study assessed U-EV profiles from individuals affected by PCa at Gleason scores 6–9, compared with healthy controls. U-EVs were characterised and assessed for proteomic cargo content by LC-MS/MS analysis. The U-EV proteomes were compared for enrichment of gene ontology (GO), KEGG, and Reactome pathways, as well as disease–gene associations. U-EVs ranged in size from 50 to 350 nm, with the majority falling within the 100–200 nm size range for all groups. U-EV protein cargoes from the PCa groups differed significantly from healthy controls, with 16 protein hits unique to the GS 6–7 and 88 hits to the GS 8–9 U-EVs. Pathway analysis showed increased enrichment in the PCa U-EVs of biological process GO (5 and 37 unique to GS 6–7 and GS 8–9, respectively), molecular function GO (3 and 6 unique to GS 6–7 and GS 8–9, respectively), and cellular component GO (10 and 22 unique to GS 6–7 and GS 8–9, respectively) pathways. A similar increase was seen for KEGG pathways (11 unique to GS 8–9) and Reactome pathways (102 unique to GS 8–9). Enrichment of disease–gene associations was also increased in the PCa U-EVs, with the highest differences for the GS 8–9 U-EVs (26 unique terms). The pathway enrichment in the PCa U-EVs was related to several key inflammatory, cell differentiation, cell adhesion, oestrogen signalling, and infection pathways. Unique GO and KEGG pathways enriched for the GS 8–9 U-EVs were associated with cell–cell communication, immune and stress responses, apoptosis, peptidase activity, antioxidant activity, platelet aggregation, mitosis, proteasome, mRNA stability, oxytocin signalling, cardiomyopathy, and several neurodegenerative diseases. Our findings highlight U-EVs as biomarkers to inform disease pathways in prostate cancer patients and offer a non-invasive biomarker tool for clinical use.
AB - Urinary extracellular vesicles (U-EVs) are gaining increasing interest as non-invasive liquid biopsy tools for clinical use. Prostate cancer (PCa) is amongst the highest cancer-related causes of death in men, and therefore, the identification of non-invasive, robust biomarkers is of high importance. This study assessed U-EV profiles from individuals affected by PCa at Gleason scores 6–9, compared with healthy controls. U-EVs were characterised and assessed for proteomic cargo content by LC-MS/MS analysis. The U-EV proteomes were compared for enrichment of gene ontology (GO), KEGG, and Reactome pathways, as well as disease–gene associations. U-EVs ranged in size from 50 to 350 nm, with the majority falling within the 100–200 nm size range for all groups. U-EV protein cargoes from the PCa groups differed significantly from healthy controls, with 16 protein hits unique to the GS 6–7 and 88 hits to the GS 8–9 U-EVs. Pathway analysis showed increased enrichment in the PCa U-EVs of biological process GO (5 and 37 unique to GS 6–7 and GS 8–9, respectively), molecular function GO (3 and 6 unique to GS 6–7 and GS 8–9, respectively), and cellular component GO (10 and 22 unique to GS 6–7 and GS 8–9, respectively) pathways. A similar increase was seen for KEGG pathways (11 unique to GS 8–9) and Reactome pathways (102 unique to GS 8–9). Enrichment of disease–gene associations was also increased in the PCa U-EVs, with the highest differences for the GS 8–9 U-EVs (26 unique terms). The pathway enrichment in the PCa U-EVs was related to several key inflammatory, cell differentiation, cell adhesion, oestrogen signalling, and infection pathways. Unique GO and KEGG pathways enriched for the GS 8–9 U-EVs were associated with cell–cell communication, immune and stress responses, apoptosis, peptidase activity, antioxidant activity, platelet aggregation, mitosis, proteasome, mRNA stability, oxytocin signalling, cardiomyopathy, and several neurodegenerative diseases. Our findings highlight U-EVs as biomarkers to inform disease pathways in prostate cancer patients and offer a non-invasive biomarker tool for clinical use.
KW - Prostate Cancer
KW - Extracellular vesicles (EVs)
KW - Protein Biomarkers
KW - U-EVs
KW - Clinical Samples
U2 - 10.3390/ijms26146895
DO - 10.3390/ijms26146895
M3 - Article
SN - 1661-6596
VL - 26
JO - International Journal of Molecular Sciences (IJMS)
JF - International Journal of Molecular Sciences (IJMS)
IS - 14
M1 - 6895
ER -