449: Differential Gene Expression in Noncancerous Prostate Tissue of Men with and without Prostate Cancer

Abstract

94 INTRODUCTION & OBJECTIVE Microarray studies have made significant contributions to the molecular classification of prostate cancer (PCA). The identification of class-specific transcriptional patterns may represent new targets for the development of new diagnostic tools and cancer therapies. We performed gene expression analysis of normal and malignant tissue samples taken from prostate cancer patients. In addition, we included normal prostate samples from an healthy control group. Our aims were to identify (1) the gene expression patterns distinguishing normal and malignant tissue and (2) the molecular signatures discriminating normal tissue from healthy males and prostate cancer patients. MATERIAL & METHODS We investigated 34 localized PCA, 34 matched normal prostate tissues from the nonmalignant region of the prostate and prostate tissue from 40 healthy male volunteers (18 - 67 y, by needle core biopsy). The samples were evaluated by histopathology. Glandular cells were isolated by laser capture microdissection and pressure catapulting (LMPC). Total RNA was isolated and quality controlled, then the RNA was amplified by T7-based RNA polymerase in vitro transcription. Gene expression profiling was performed by hybridization of the labeled samples onto human whole genome cDNA-Microarrays encompassing 37,531 cDNA clones (Human Unigene Set RZPD3.1). For following quantification we performed real-time PCR, using TaqMan probes on an ABI Prism 7000 sequence detection system (Applied Biosystems). RESULTS The analyses resulted in gene expression profiles distinguishing significantly tumor from matched normal tissue samples. Many of the genes were found deregulated in accordance with known literature data, while others had not yet been associated with prostate cancer. There was a clear gene expression pattern distinguishing normal tissue (PCA patients) from the tissue of healthy male. While the normal samples showed large molecular inter-individual variation, gene expression in the healthy samples was highly homogeneous. CONCLUSIONS We demonstrate specific gene expression differences between normal prostate tissue from PCA patients and tissue from healthy males. The identified gene expression patterns could be used for the diagnosis of prostate tumors based on the gene expression in histological non-cancerous prostate tissue.