Hormone refractory
prostate cancer (PCa) is invariably lethal despite aggressive clinical treatment strategies. Detection strategies are needed to identify aggressive PCa before it becomes widely disseminated. Recently, two studies identified
annexin 1 and 7 as potential
biomarkers in the development of PCa progression. The
annexins are a group of
calcium-binding structural
proteins that may play a role in the regulation of membrane trafficking, cellular adhesion, and cell signaling. Therefore the goal of this study is to simultaneously characterize the multiple members of the
annexin family of genes in advanced PCa. Prostate samples from men with advanced
hormone refractory PCa were compared to samples of
hormone-naïve PCa and noncancerous prostate tissue. Samples from 15 patients with advanced
hormone refractory PCa were used. To examine the
annexin family, gene expression profiles from 21 noncancerous prostate tissues, 16 clinically localized PCas, and 20
hormone refractory PCa samples were used. By
cDNA microarray analysis,
annexins 1, 2, 4, 7, and 11 were significantly decreased in
hormone refractory PCa when compared to localized
hormone-naïve PCa with 2.2-, 1.5-, 1.3-, 1.4-, and 1.8-fold decreases, respectively (all P values <0.05). Interstudy validation of
annexin family transcript expression was performed by meta-analysis of three other published prostate profiling studies. High-density tissue microarrays were used to validate a subset of
annexins at the
protein level by immunohistochemistry. Tissue microarray analysis revealed a significant decrease in
protein expression for
annexins 1, 2, 4, 7, and 11 in
hormone refractory PCa as compared to localized PCa with 1.68-, 2.46-, 2.52-, and 3.01-fold decreases, respectively (Kruskal Wallis test, all P values P < 0.05). However, no significant differences were detected between the clinically localized PCa and noncancerous prostate tissues. These findings suggest that down-regulation of several members of the
annexin family may contribute to PCa
tumorigenesis.
Annexins 1, 2, 4, 7, and 11 may play a role in
tumor progression through distinct mechanisms or, alternatively, they may have redundant
tumor suppressor activities. This study also suggests that a meta-analysis of existing gene expression data is useful in confirming findings from individual studies. Finally, down-regulation of several
annexin family members may play a role in the development of the lethal PCa phenotype.