Human prostate cancer and benign prostatic hyperplasia: Molecular dissection by gene expression profiling

Critical aspects of the biology and molecular basis for prostate malignancy remain poorly understood, To reveal fundamental differences between benign and malignant growth of prostate cells, we performed gene expression profi ling of primary human prostate cancer and benign prostatic hyperplasia (BPH ) using cDNA microarrays consisting of 6500 human genes. Frozen prostate sp ecimens were processed to facilitate extraction of RNA from regions of tiss ue enriched in either benign or malignant epithelial cell growth within a g iven specimen. Gene expression in each of the 16 prostate cancer and nine B PH specimens was compared with a common reference to generate normalized me asures for each gene across all of the samples. Using an analysis of comple te pairwise comparisons of expression profiles among all of the samples, we observed clearly discernable patterns of overall gene expression that diff erentiated prostate cancer from BPH, Further analysis of the data identifie d 210 genes with statistically significant differences in expression betwee n prostate cancer and BPH, These genes include many not recognized previous ly as differentially expressed in prostate cancer and BPH, including hepsin , which codes for a transmembrane serine protease, This study reveals for t he first time that significant and widespread differences in gene expressio n patterns exist between benign and malignant growth of the prostate gland. Gene expression analysis of prostate tissues should help to disclose the m olecular mechanisms underlying prostate malignant growth and identify molec ular markers for diagnostic, prognostic, and therapeutic use.