After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen independent (AI) cancer. The molecular mechanisms underlying progression are not well known, in part due to the rarity of AI samples from primary and metastatic sites.
We compared the gene expression profiles of ten AI primary prostate tumor biopsies with ten primary, untreated androgen-dependent (AD) tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A Gene Chips. Differential expression was examined with principle component analysis (PCA) and Student t testing. Analysis of gene ontology was performed with Expression Analysis Systematic Explorer (EASE) and gene expression data were integrated with genomic alterations with DIfferential Gene locus MAPping (DIGMAP).
Unsupervised PCA showed that the AD and AI tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between AI and AD tumors: macromolecule biosynthesis was down-regulated and cell adhesion up-regulated in AI tumors. Other differentially expressed genes were related to IL-6 signaling, as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The DIGMAP analysis identified nine regions of potential chromosomal deletion in the AI tumors including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21.
Taken together, these data identify several unique characteristics of AI prostate cancer that may hold potential for the development of targeted therapeutic intervention.