Pd35-11 Neutrophil-Related Urinary Extracellular Vesicle Protein Signatures May Predict Late Radiation Cystitis Risk in Prostate Cancer Patients

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-11 NEUTROPHIL-RELATED URINARY EXTRACELLULAR VESICLE PROTEIN SIGNATURES MAY PREDICT LATE RADIATION CYSTITIS RISK IN PROSTATE CANCER PATIENTS Ryan D. Molony, M. Mahmudul Hasan Akash, Sarah L. Kerns, Brian Marples, Emmanuel Oshodi, YuhChyau Chen, and Yi-Fen Lee Ryan D. MolonyRyan D. Molony , M. Mahmudul Hasan AkashM. Mahmudul Hasan Akash , Sarah L. KernsSarah L. Kerns , Brian MarplesBrian Marples , Emmanuel OshodiEmmanuel Oshodi , YuhChyau ChenYuhChyau Chen , and Yi-Fen LeeYi-Fen Lee View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: After undergoing radiotherapy (RT), ∼15% of prostate cancer (PCa) patients develop late radiation cystitis (RC), presenting principally as hematuria, but the mechanisms underlying this pathological outcome remain poorly characterized. Membrane-enclosed extracellular vesicles (EVs) are released from tumor and non-tumor cells at baseline, and their composition can change markedly in response to stimuli. We recently found that elevated post-RT PCa patient urinary EV concentrations can predict RC incidence 6+ months after sample collection, suggesting a possible role for these EVs as biomarkers and/or functional mediators of RC incidence. Here, we sought to characterize the composition of pre- and post-RT urinary EVs from PCa patients to understand their association with bladder tissue toxicity. METHODS: Urinary EV cargo proteins in pre- and post-RT PCa patient samples for patients that did and did not develop late hematuria were analyzed and compared by LC-MS/MS. Proteomic analyses were used to identify enriched proteins (≥10-fold change in abundance) between donors that did and did not develop RC. ELISAs were used to measure the levels of myeloperoxidase (MPO) and inflammatory cytokines (TNF-α, IL-6, IL-1β) in PCa patient samples. RESULTS: Relative to patients who did not develop RC, the post-RT urinary EVs of PCa patients who eventually developed RC harbored significantly elevated levels of 40 RT-enriched proteins, including a high number of neutrophil-associated marker and effector proteins with potential pro-inflammatory and deleterious functions. Strikingly, an intrinsically enriched 20-protein signature was also detected in the pre-RT urinary EVs of PCa patients who went on to develop post-RT hematuria, and this signature was dominated by neutrophil proteins, including MPO. ELISAs confirmed the presence of higher MPO and inflammatory cytokine levels in urine samples from PCa patients who later developed hematuria. CONCLUSIONS: These data highlight a potential role for neutrophil EVs present in urine as biomarkers and/or mediators of late hematuria and RC incidence in PCa patients. While further large-scale validation of these results will be essential, the intrinsically enriched 20-protein signature established herein may provide an opportunity for PCa patient risk stratification before treatment, while the 40-protein RT-enriched protein signature may support post-RT monitoring, enabling treatment modification or other interventions that can abrogate decisional regret and improve quality of life. Source of Funding: Funded by the Department of Urology Research Fund © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e729 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ryan D. Molony More articles by this author M. Mahmudul Hasan Akash More articles by this author Sarah L. Kerns More articles by this author Brian Marples More articles by this author Emmanuel Oshodi More articles by this author YuhChyau Chen More articles by this author Yi-Fen Lee More articles by this author Expand All Advertisement PDF downloadLoading ...