Mp05-03 Urinary Extracellular Vesicle Proteins as Signatures for Cribriform and Intraductal Prostate Carcinoma

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-03 URINARY EXTRACELLULAR VESICLE PROTEINS AS SIGNATURES FOR CRIBRIFORM AND INTRADUCTAL PROSTATE CARCINOMA Rui Miguel Marques Bernardino, Ana Sofia Carvalho, Luis Campos Pinheiro, Rashid Sayyid, Ricardo Leao, Hans Beck, Hermínia Pereira, Rui Henrique, Neil Fleshner, and Rune Matthiesen Rui Miguel Marques BernardinoRui Miguel Marques Bernardino , Ana Sofia CarvalhoAna Sofia Carvalho , Luis Campos PinheiroLuis Campos Pinheiro , Rashid SayyidRashid Sayyid , Ricardo LeaoRicardo Leao , Hans BeckHans Beck , Hermínia PereiraHermínia Pereira , Rui HenriqueRui Henrique , Neil FleshnerNeil Fleshner , and Rune MatthiesenRune Matthiesen View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current imaging and diagnostic tools perform poorly for the reliable prediction of presence of intraductal carcinoma and cribriform pattern at prostate biopsy. The presence of those patterns has been consistently demonstrated to be associated with adverse prostate cancer outcomes, including increased risks of biochemical recurrence, metastasis, and cancer-specific mortality. The main objective of this study is to identify a biomarker for PCa patients with cribriform pattern and intraductal PCa (IDC). METHODS: Urinary small extracellular vesicle (EV) proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-MS/MS). Small EVs isolated from urine of healthy donors (HD), patients without cribriform and IDC histological prostate patterns submitted to radical prostatectomy (non-IDC/non-Crib), and patients with cribriform and/or IDC histological prostate patterns (IDC/Crib) were analyzed by bottom-up proteomics. RESULTS: We identified 171 proteins that were differentially expressed between IDC/Crib and non-IDC/non- Crib after correction for multiple testing. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle suggesting high heterogeneity. Overall the urinary EV proteome appears to reflect the prostate pathology. TMBIM1, also known as Bax inhibitor 1 (BI-1), was among those most upregulated in Crib and IDC compared to cancer without IDC/Crib. CONCLUSIONS: BI-1, plays a crucial role in regulating apoptosis and calcium homeostasis by inhibiting the activity of the pro-apoptotic protein Bax and protecting cells from apoptosis induced by various stimuli. Bax inhibitor-1 specific down-regulation by RNA interference leads to cell death in human PCa cells. TMBIM1 has also been previously identified as up-regulated in urinary EVs in patients with high-grade prostate cancer (poor prognosis). Based on our analysis, we conclude that the proteome of small urinary EVs holds diagnostic potential and appears to reflect the proteome of prostate tissue. Urinary EV proteome highlighted proteins with a role in androgen response, epithelial mesenchymal transition, fatty acid metabolism and reactive oxygen species as prognostic factors for prostate cancer. Source of Funding: RB has a FCT PhD grant (BD2022.13386)This project was funded by Liga Portuguesa Contra o Cancro - Terry Fox Grant © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e43 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Rui Miguel Marques Bernardino More articles by this author Ana Sofia Carvalho More articles by this author Luis Campos Pinheiro More articles by this author Rashid Sayyid More articles by this author Ricardo Leao More articles by this author Hans Beck More articles by this author Hermínia Pereira More articles by this author Rui Henrique More articles by this author Neil Fleshner More articles by this author Rune Matthiesen More articles by this author Expand All Advertisement PDF downloadLoading ...