Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study

• Published in: Scientific reports Vol. 14; no. 1; pp. 25065 - 16
• Main Authors: Bernardino, Rui, Carvalho, Ana Sofia, Hall, Michael J., Alves, Liliana, Leão, Ricardo, Sayyid, Rashid, Pereira, Hermínia, Beck, Hans Christian, Pinheiro, Luís Campos, Henrique, Rui, Fleshner, Neil, Matthiesen, Rune
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/475; 631/67/2322; 631/67/327; Aged; Biomarkers, Tumor - urine; Biopsy; Chromatography, Liquid; Cribriform; Cross-Sectional Studies; Extracellular vesicles; Extracellular Vesicles - metabolism; Gene set enrichment analysis; Heterogeneity; Humanities and Social Sciences; Humans; Intraductal prostate carcinoma; Liquid chromatography; Liquid chromatography mass spectrometry; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; multidisciplinary; Neoplasm Grading; Pathology; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - urine; Proteins; Proteome - analysis; Proteomes; Proteomics; Proteomics - methods; Science; Science (multidisciplinary); Tandem Mass Spectrometry; Urinary extracellular vesicles and particles; Urinary extracellular vesicles and particles; Cribriform; Intraductal prostate carcinoma; Liquid chromatography mass spectrometry; Proteomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-75272-w

Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. 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 proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.