Study on expression of brca1 and brca2 genes in carcinoma prostate and its correlation with histopathology

Abstract

Introduction: Prostate cancer is one of the most prevalent cancers in men worldwide, with increasing incidence noted particularly in regions like India. Tumor suppressor genes such as BRCA1 and BRCA2, which are essential for genomic stability, have been implicated in prostate cancer progression. Elevated PSA levels and higher Gleason scores further correlate with aggressive tumor phenotypes. In addition, computational methods, including molecular docking, offer insights into protein–protein interactions that may aid in identifying novel therapeutic targets. Objectives: 1. To assess mRNA expression of BRCA1 and BRCA2 genes in carcinoma prostate and its correlation with PSA levels and Gleason score. 2. To study in silico analysis of BRCA 1 and BRCA 2 in relation to prostate specific antigen (PSA) like human kallikreins (hK1, hK2, hK3 and hK4). Methods: A prospective observational study was conducted involving prostate tissue samples from patients diagnosed with carcinoma prostate and Benign Prostatic Hyperplasia (BPH). RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) samples and reverse transcribed to cDNA. Quantitative PCR (qPCR) was employed to quantify BRCA1 and BRCA2 expression, normalized to GAPDH using the ΔΔCT method. Statistical analyses, including Spearman’s rank correlation and ANOVA, were used to correlate gene expression with PSA levels and Gleason grades. Additionally, molecular docking simulations were performed using AutoDock 4.2 and visualized with Discovery Studio to evaluate the binding affinities between BRCA proteins and kallikrein peptides. Results: The qPCR analysis revealed a statistically significant under expression of both BRCA1 and BRCA2 in carcinoma prostate samples compared to BPH controls. A significant negative correlation was observed between PSA levels and BRCA2 expression, while BRCA1 showed a less pronounced relationship. Moreover, a progressive decline in mRNA expression of both genes was noted with increasing Gleason grades, suggesting an association with tumor aggressiveness. Molecular docking studies demonstrated favorable binding interactions between BRCA proteins and kallikreins, highlighting potential avenues for targeted therapeutic interventions. Conclusion: The findings underscore the clinical relevance of BRCA1 and BRCA2 as molecular markers in prostate cancer, where their underexpression is linked with higher PSA levels and more aggressive Gleason grades. The molecular docking results further suggest that interactions between BRCA proteins and PSA like kallikreins could be used to predict expression of BRCA1 and BRCA2 along with development of targeted therapies, supporting the integration of genetic and computational approaches in prostate cancer management.