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

Abstract

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.

• Authors: Ryutaro Mori, Tanya B Dorff, Shigang Xiong, Chad J Tarabolous, Wei Ye, Susan Groshen, Kathleen D Danenberg, Peter V Danenberg, Jacek K Pinski
• Journal: The Prostate (Prostate) Vol. 70 Issue 15 Pg. 1692-700 (Nov 01 2010) ISSN: 1097-0045 [Electronic] United States
• PMID: 20564320 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• AR protein, human
• Androgen Antagonists
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• Receptors, Androgen
• VEGFA protein, human
• VEGFC protein, human
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor C

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis, genetics)
• Male
• Middle Aged
• Neoplasm Staging
• Neoplasms, Hormone-Dependent (genetics, metabolism, pathology, therapy)
• Neovascularization, Pathologic (drug therapy, genetics, metabolism, pathology)
• Prognosis
• Proportional Hazards Models
• Prostatectomy
• Prostatic Neoplasms (genetics, metabolism, pathology, therapy)
• RNA, Messenger (biosynthesis, genetics)
• Receptors, Androgen (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Statistics, Nonparametric
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)
• Vascular Endothelial Growth Factor C (biosynthesis, genetics)