Expression analysis of VEGF-A and VEGF-B: Relationship with clinicopathological parameters in bladder cancer

Abstract

Abstract. The present investigation was conducted first to determine whether correlation exists between VEGF-A and -B mRNA levels and clinicopathological parameters and to assess their prognostic value in bladder cancer, then to clarify the expression level and biological significance of VEGF-A isoforms. Total RNA was isolated from 37 specimens of bladder cancer. Northern blot analysis revealed that VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer and detected three VEGF-A transcripts of 5.2, 4.5 and 1.7 kb in length, respectively. The VEGF-A transcript levels were greater in cancer tissues than in normal urothelium. They were significantly higher in pT2-T4 than in pTa and pT1 urothelial tumors and thus, were correlated to the pathologic stage. Contrary to the 4.5 kb transcript, elevated expression of the 5.2 and 1.7 kb transcripts was correlated with the histologic grade and the presence of carcinoma in situ. Patients with higher VEGF-A mRNA levels had a significantly shorter survival without progression compared to those with lower levels. Three VEGF-A splice variants were detected by Southern blotting namely, VEGF121, 165 and 189. The expression intensity of each isoform was evaluated by quantitative real-time RT-PCR in 20 new fresh frozen recent tumors. VEGF121 and VEGF165 were expressed at the similar level. On the contrary, they were significantly more expressed than VEGF189 (p<0.05). The three isoforms were higher expressed in pT2 bladder cancers than in pTa tumors (p<0.05). There was only a significant correlation between the increased expression level of VEGF121 and 165 and the histological grade of the lesion (p<0.05). To conclude, VEGF-A mRNA level is a potential prognostic indicator of progression in bladder cancer as well as the expression level of the different VEGF-A splice variants.

Chemoprevention of Urothelial Cell Carcinoma Growth and Invasion by the Dual COX–LOX Inhibitor Licofelone in UPII-SV40T Transgenic Mice

“…It correlated with the histologic grade and the presence of carcinoma in situ . Patients with higher VEGF had a significantly shorter progression-free survival compared with those with lower levels (43). Elevated levels of VEGF and its receptors were found in bladder cancer specimens and expression correlated with the invasiveness (44).…”

A Novel Molecular Grading Model: Combination of Ki67 and VEGF in Predicting Tumor Recurrence and Progression in Non-invasive Urothelial Bladder Cancer

“…On the other hand, tumor vascularization plays a fundamental role in neoplastic processes and is essential for tumor progression and the metastatic spread of solid tumors (Vidal et al, 2008). Vascular Endothelial Growth Factor (VEGF) is considered one of the most important angiogenic regulators during tumor angiogenesis (Fauconnet et al, 2009). VEGF is expressed in both invasive and noninvasive bladder tumors, and the increased expression of VEGF is associated with higher tumor stage and progression, but similarly to the circumstance of Ki67, a definite cut-off point for stratifying a better or worse prognosis remains unclear.…”

Emerging antibody-based therapeutic strategies for bladder cancer: A systematic review

“…These proteins have emerged as key regulators of embryonic angiogenesis, as well as of the neoangiogenesis process in cancer and other diseases ( Figure 3) [75][76][77]. Both VEGF and VEGFR have been described as overexpressed and associated with a malignant phenotype bladder cancer cell models and tissues [78,79], and also with tumor progression, invasion and poor prognosis in clinical studies [79][80][81].…”