Prostate Tumor Heterogeneity and Obesity: A Transcriptomic and Proteomic Analysis of Patients with Different BMIs

• Grant number: 25/27589-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2026
• End date: March 31, 2029
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Sérgio Luis Felisbino
• Grantee: Sérgio Luis Felisbino
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• City of the host institution: Botucatu
• Associated researchers: Flávio de Oliveira Lima ; Mariana Pereira Antoniassi ; Tiago Aparecido Silva

Abstract

Prostate cancer (PCa) is one of the leading causes of male cancer mortality worldwide and the second most common cancer in Brazil, with an estimated 71,730 new cases per year in the 2023-2025 triennium. Obesity, which affects more than 22% of the Brazilian adult population, is associated with chronic inflammatory states that favor tumor progression. Considering this relationship, this project aims to characterize the transcriptomic and proteomic profile of normal and tumorous prostate tissues from patients with different body mass indices, seeking to identify gene and protein expression patterns associated with excess weight. 150 samples from 50 patients who underwent total prostatectomy will be used, three per patient: one normal adjacent to the tumor (NAT) and two tumor samples, both staged by histopathological analysis. DNA, RNA, and proteins will be extracted and quantified. Messenger RNAs from the samples will be sequenced by NGS. The proteomic profile will be determined by mass spectrometry. The raw data will be processed, being aligned to the human genome, quantifying transcripts, identifying differentially expressed genes (DEGs) and differentially expressed proteins by abundance. Functional enrichment assessment (GO, KEGG) and construction of protein-protein interaction networks (STRING) will be performed. For functional validation, the most relevant differentially expressed genes and proteins will be silenced in prostate cell lines (PNT2, LNCaP and PC3) with siRNA, followed by cell viability assays (MTT), migration (wound healing), RT-qPCR and immunofluorescence. It is expected to identify molecular signatures associated with excess weight and tumor aggressiveness, with the potential to suggest biomarkers and new therapeutic strategies for obese patients with prostate cancer, contributing to advances in precision medicine. (AU)