
CD31 Expression in Prostate Cancer
Sina Shahshenas 1, Daniel Shahi 1 ℗, Hossein Yarmohammadi 2, Masood Soltanipur 3, Mohammadreza Jalali Nadoushan 4 ©
Abstract
Introduction: Prostate cancer remains one of the leading causes of cancer-related morbidity and mortality among men. Angiogenesis plays a crucial role in tumor growth, progression, and metastasis. CD31, also known as Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), is a well-established marker of endothelial cells and is commonly used to assess microvessel density (MVD) in tumor tissues. Increased CD31 expression may reflect heightened angiogenic activity, which is associated with aggressive tumor behavior. This study aims to evaluate CD31 expression in prostate cancer tissues. Materials and Methods: This study included 78 prostate cancer patients. Immunohistochemistry (IHC) was performed to assess CD31 expression. Tumor areas with the highest density of positive endothelial cells were identified on slides, and MVD was counted in 10 high-power fields (400× magnification). Each stained endothelial cell or cluster was counted as one microvessel. MVD was defined as the sum of the three highest counts. Expression levels above 85 were considered positive, while lower levels were negative. Correlations between CD31 expression, Gleason score, and grade were analyzed. Additionally, RNA expression and clinical data from 500 prostate cancer samples (TCGA-PRAD) were analyzed. After quality control and normalization, co-expression networks were constructed with WGCNA. Pathway enrichment analyses (GO & KEGG) were performed. Results: IHC analysis showed that 24 out of 78 prostate cancer samples were CD31-positive. Patients with CD31+ tumors had a slightly higher mean age (71.75 ± 8.43 years) compared to CD31- cases (70.26 ± 8.91 years), but this difference was not statistically significant (p=0.490). However, CD31+ tumors were associated with significantly higher Gleason grades (3.08 ± 1.47 vs. 2.24 ± 1.18, p=0.018) and Gleason scores (7.5 ± 1.02 vs. 6.85 ± 0.79, p=0.009). Linear regression analysis revealed significant positive correlations between CD31 expression and Gleason grade (R=0.418, R²=0.175, p0.05) as well as Gleason score (R=0.454, R²=0.206, p0.05). Analysis of the TCGA-PRAD dataset using WGCNA identified CD31 as a key gene in the "purple" module. Pathway enrichment analysis showed significant involvement of this module in cell adhesion and angiogenesis pathways. Furthermore, gene expression within this module was significantly higher in tumors with Gleason grade 5. For predicting high-grade tumors (Grade 3), CD31 showed an AUC of 0.767 (p 0.001) Conclusion and Discussion: This study demonstrates that increased CD31 expression is significantly associated with higher Gleason grade and score in prostate cancer, indicating its potential role as a marker of tumor aggressiveness. The identification of CD31 as a key gene in angiogenesis and cell adhesion pathways further supports its involvement in prostate cancer progression. These findings suggest that CD31 could serve as a valuable prognostic biomarker.
Keywords: Prostate cancer; Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1); CD31; Gleason