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Proteomics. 2019 Oct 1:e1900174. doi: 10.1002/pmic.201900174. [Epub ahead of print]

Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia.

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Instituto de Ciências Biomédicas, Departamento de Parasitologia, Universidade de São Paulo, USP, São Paulo, Brazil.
Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia.
Laboratório de Investigação Médica da Disciplina de Urologia da Faculdade de Medicina da USP, LIM55, São Paulo, Brazil.
Instituto de Química, Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.


Prostate cancer (PCa) remains a prevalent and deadly disease. The histology-based Gleason score (GS) of PCa tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide decision-making with respect to treatment strategies and patient management. However, inherent variability associated with PCa tumour sampling and the subjective determination of the GS are still key challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are urgently needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, we have used label-free LC-MS/MS-based proteomics to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to five tissues from individuals with benign prostatic hyperplasia (BPH). Over 2,000 proteins were consistently identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. Excitingly, a panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, CTSZ displayed the potential to accurately stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validated the differential expression of four of the 11 proteins, LMOD1, GYG1, IGKV3D-20 and RNASET2. This is the first study to characterise the prostate tissue proteome signatures related to the five PCa grades and BPH. The four proteins associated with low and high PCa grades reported here for the first time warrant further exploration as candidate biomarkers for PCa aggressiveness. This article is protected by copyright. All rights reserved.


aggressiveness; biomarker; gleason score; grades; mass spectrometry; prostate cancer; proteome; proteomics


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