Investigation of angiogenesis and epithelial-mesenchymal transition markers (CD31, VEGF, and E-Cadherin) in prostatic cancer patients: a multi-omics study.

backgroundProstate cancer (PCa) progression is critically driven by angiogenesis and epithelial–mesenchymal transition (EMT), processes that facilitate tumor growth, invasion, and metastasis. However, the coordinated roles of the endothelial marker CD31 (PECAM1), VEGF, and E-cadherin in PCa aggressiveness remain to be fully elucidated. Here, we investigated the relationships among these biomarkers, Gleason score, and tumor grade, and integrated immunohistochemical (IHC) findings with transcriptomic analyses.

methodsSeventy-eight prostate adenocarcinoma specimens obtained via radical prostatectomy or transurethral resection (2020–2025) underwent IHC staining for CD31, VEGF, and E-cadherin. Marker expression was quantified by labeling indices, Final Staining Score (FSS), and semi-quantitative scoring, then correlated with Gleason score and grade using appropriate statistical tests (ANOVA, Mann–Whitney U, Kruskal–Wallis, correlation, logistic regression, and ROC analysis). Bioinformatic analyses of 500 TCGA-PRAD RNA-seq samples included Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules and hub genes, Differential gene expression (DEG), and Gene Set Enrichment Analysis (GSEA) to assess pathway enrichment.

resultsCD31 positivity was observed in 30.8% of cases and was associated with significantly higher Gleason scores and grades (p < 0.01). VEGF FSS increased stepwise with grade (p < 0.001), while E-cadherin expression inversely correlated with tumor aggressiveness (p < 0.001). Individually, CD31 and VEGF yielded AUCs of 0.767 and 0.680, respectively, for discriminating Gleason > 7, whereas E-cadherin loss provided the strongest inverse predictive value. The logistic regression model, integrating age with immunohistochemical expression of E-cadherin, VEGF and CD31, demonstrated strong discriminatory performance for distinguishing high-grade from low-grade tumors (AP 0.90, AUC 0.95). WGCNA identified PECAM1 as a hub in an angiogenesis-enriched module, and GSEA confirmed upregulation of angiogenic and EMT programs in high-grade tumors.

conclusionHigh-grade PCa is characterized by enhanced angiogenesis (CD31, VEGF) and loss of epithelial adhesion (E-cadherin), underscoring the interplay of vascularization and EMT in tumor progression. These markers, individually and in combination, may inform prognostic stratification and represent potential therapeutic targets.