The relationship between proangiogenic gene expression levels in prostate cancer and their prognostic value for clinical outcomes.

BACKGROUND

Androgens stimulate the expression of vascular endothelial growth factor (VEGF) through activation of hypoxia inducible factor (HIF). These genes play a major role in cancer angiogenesis. This study assesses the relationship among expression levels for the androgen receptor (AR), HIF1a, VEGF-A, and VEGF-C genes in human prostate cancer tissue and their impact on prostate cancer outcomes. It also examines the impact of pre-operative androgen deprivation therapy (ADT) on the expression of these genes.

METHODS

Radical prostatectomy specimens were obtained from 138 patients with D1 prostate cancer from the University of Southern California prostatectomy database; 30% received pre-operative and 23% received post-operative ADT. Gene expression levels were determined by quantitative real-time PCR. Specimens were stratified into three groups for each gene based on expression levels, and groups were compared for clinical outcomes (PSA and clinical recurrence, overall survival).

RESULTS

There was a significant correlation in expression levels amongst all genes. Patients treated with pre-operative ADT had significantly lower HIF1a expression, mean 2.64 (CI 2.34-2.94) than patients not treated, mean 3.25 (CI 2.97-3.53, P = 0.006), adjusting for age, PSA, Gleason score, and stage. Higher VEGF-A expression was significantly associated with better overall survival (HR 0.49, P = 0.015). The risk of developing clinical recurrence was significantly lower with higher VEGF-C expression (HR 0.4, P = 0.014).

CONCLUSIONS

Significant correlation was noted among AR, HIF1a, VEGF-A, and VEGF-C. This study shows that ADT is associated with lower HIF1a gene expression in human prostate cancer tissue and documents prognostic value for VEGF-A and VEGF-C expression levels.