Biomarkers for Prostate Cancer Aggressiveness in Puerto Rican Men: Analysis of Phospho-Rb S249, N-cadherin, β-catenin, and E-cadherin Expression in Prostate Biopsies

Prostate cancer (PCa) is the leading cause of cancer in Puerto Rican men and exhibits significant racial disparities globally. Although only 8% of cases invade beyond the prostate, predicting PCa aggressiveness is challenging. This study investigated the potential of the retinoblastoma tumor suppressor protein phosphorylated in Serine 249 (Phospho-Rb S249), N-cadherin, β-catenin, and E-cadherin as biomarkers for identifying aggressive PCa in Puerto Rican men. We hypothesized that the expression of these proteins could serve as biomarkers for identifying PCa tumors with potential to becoming aggressive in Puerto Rican men. Immunohistochemistry was performed on 23 biopsies from Puerto Rican men to evaluate the biomarkers' expression, and correlation analyses examined associations with clinicopathological parameters. Results showed that Phospho-Rb S249 expression correlated positively with tumor size and positive cores in patients with Gleason scores ≥4+3. β-catenin was positively associated with tumor size and carcinoma percentage in Gleason scores ≥4+3. E-cadherin expression negatively correlated with grade group, indicating a protective role. In contrast, N-cadherin and β-catenin were more prominent in Gleason scores ≤3+4, hinting at their involvement in early epithelial-to-mesenchymal transition (EMT). A decision tree analysis identified N-cadherin expression as a key determinant for classifying PCa aggressiveness, with an 82% likelihood. These findings suggest N-cadherin as a biomarker for identifying PCa with the potential to become aggressive. While our study provides promising results, further validation in a larger patient cohort is needed to increase the robustness and reliability of our findings. Also, combining multiple biomarkers could further enhance the specificity of aggressive PCa detection.