مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Epithelial-Mesenchymal Transition and Angiogenesis in Prostate Cancer
Epithelial-Mesenchymal Transition and Angiogenesis in Prostate Cancer
Sina Shahshenas,1Mohammadreza Jalali Nadoushan,2,*Hossein Yarmohammadi,3Masood Soltanipur,4
1. Student Research Committee, Faculty of Medicine, Shahed University, Tehran, Iran. 2. Department of Pathology, Faculty of Medicine, Shahed University, Tehran, Iran. 3. Student Research Committee, Faculty of Medicine, Shahed University, Tehran, Iran. 4. General Practitioner (GP), Ebne-sina Medical Center (EMC), Tehran, Iran.
Introduction: Angiogenesis and epithelial–mesenchymal transition (EMT) are major drivers of prostate cancer progression, promoting tumor growth, invasion, and spread. The combined contribution of the endothelial marker CD31 (PECAM1), VEGF, and the adhesion molecule E-cadherin to tumor aggressiveness is not yet fully understood. In this study, we explored how these markers relate to Gleason score and tumor grade by integrating immunohistochemical (IHC) data with transcriptomic analyses.
Methods: Seventy-eight prostate adenocarcinoma specimens, collected via radical prostatectomy or transurethral resection between 2020 and 2025, were immunohistochemically stained for CD31, VEGF, and E-cadherin. Expression was measured using labeling indices, a Final Staining Score (FSS), and semi-quantitative scoring, then compared with Gleason score and tumor grade using appropriate statistics (ANOVA, Mann–Whitney U, Kruskal–Wallis, correlation, linear regression, and ROC analysis). For transcriptomic validation, bioinformatic analyses of 500 TCGA-PRAD RNA-seq samples were performed, including Weighted Gene Co-expression Network Analysis (WGCNA) to detect gene modules and hub genes, differential expression analysis (DEG), and Gene Set Enrichment Analysis (GSEA) to identify enriched pathways.
Results: CD31 was positive in 30.8% of specimens and was significantly associated with higher Gleason scores and tumor grades (p < 0.01). VEGF Final Staining Score rose in a stepwise manner with increasing grade (p < 0.001), while E-cadherin expression showed a strong inverse correlation with tumor aggressiveness (p < 0.001). As single biomarkers, CD31 and VEGF produced AUCs of 0.767 and 0.680, respectively, for discriminating Gleason >7, whereas loss of E-cadherin provided the strongest inverse predictive signal. Multimarker models enhanced prognostic performance: the full three-marker model explained adjusted R² = 0.427 for grade and adjusted R² = 0.473 for Gleason score. WGCNA identified PECAM1 (CD31) as a hub gene in an angiogenesis-enriched module, and GSEA confirmed upregulation of angiogenic and EMT programs in high-grade tumors.
Conclusion: High-grade prostate cancer is marked by intensified angiogenesis, reflected by increased CD31 and VEGF, and by loss of epithelial adhesion through reduced E-cadherin, highlighting a coordinated role for vascular remodeling and EMT in tumor progression. Individually and combined, these markers have potential to refine prognostic stratification and to serve as therapeutic targets.