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.
Scientific reports. 2024 Oct 23*** epublish ***
Rui Bernardino, Ana Sofia Carvalho, Michael J Hall, Liliana Alves, Ricardo Leão, Rashid Sayyid, Hermínia Pereira, Hans Christian Beck, Luís Campos Pinheiro, Rui Henrique, Neil Fleshner, Rune Matthiesen
Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal. ., Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal. ., Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal., Cuf Hospitais, Lisbon, Portugal., Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Department of Pathology, Centro Hospitalar E Universitário Lisboa Central, Lisbon, Portugal., Centre for Clinical Proteomics, Department of Clinical Biochemistry, Odense University Hospital, 5000, Odense, Denmark., Department of Urology, Centro Hospitalar e Universitário Lisboa Central, Lisbon, Portugal., Department of Pathology and Cancer Biology and Epigenetics Group - Research Center of IPO Porto (CI-IPOP) / RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) / Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal., Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal. .