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

Author(s)

Kawahara, Rebeca ^{[1, 2]} ; Recuero, Saulo ^[3] ; Nogueira, Fabio C. S. ^[4] ; Domont, Gilberto B. ^[4] ; Leite, Katia R. M. ^[3] ; Srougi, Miguel ^[3] ; Thaysen-Andersen, Morten ^[2] ; Palmisano, Giuseppe ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, BR-05508000 Sao Paulo - Brazil

^[2] Macquarie Univ, Dept Mol Sci, Sydney, NSW 2109 - Australia

^[3] Univ Sao Paulo, LIM55, Fac Med, Lab Invest Med Disciplina Urol, BR-01246903 Sao Paulo - Brazil

^[4] Univ Fed Rio De Janeiro, Dept Bioquim, Inst Quim, BR-21941909 Rio De Janeiro - Brazil

• Document type: Journal article
• Source: PROTEOMICS; v. 19, n. 21-22, SI NOV 2019.
• Web of Science Citations: 0

Abstract

The histology-based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label-free LC-MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D-20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness. (AU)

• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support type: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 15/02866-0 - DISCOVERY AND VERIFICATION OF INTACT GLYCOPEPTIDES AS CANDIDATE PROSTATE CANCER BIOMARKERS USING MASS SPECTROMETRY-BASED PROTEOMICS APPROACHES
• Grantee: Rebeca Kawahara Sakuma
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support type: Multi-user Equipment Program
• FAPESP's process: 17/03010-8 - Site-specific characterization of N- and O-linked glycosylation in prostate cancer tissues as molecular signature for disease progression
• Grantee: Rebeca Kawahara Sakuma
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support type: Research Grants - Young Investigators Grants