Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array

BACKGROUND. To understand the molecular mechanisms underlying prostate cancer we have utilized the gene expression array to search for genes whose expression is altered in this disease. METHODS. RNA quality from manual microdissected tissue was compared with that from microselected tissue by electrophoresis. For array analysis, malignant and normal prostate epithelium was enriched using microselection technique from prostate cancer and the peripheral zone of a normal prostate. Identical array membrane was hybridized to labeled cancer and normal cDNA, respectively. The differentially expressed gene was further evaluated by RT-PCR. RESULTS. Microdissection, but not microselection, causes visible degradation to RNA. Of the 588 genes on the membrane, 87 genes yielded significant signals. Based on a three fold difference relative to normal prostate tissue, 1 gene was overexpressed and 12 genes underexpressed in prostate cancer. Of them, five showed statistically significant reduction in mRNA levels in six prostate cancer specimens compared with seven normal prostate specimens. These five genes are glutathione S-transferase M1 (GSTM1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha receptor-1 (TNFR-1), transforming growth factor beta3 (TGF-beta3), and inhibitor of DNA binding-1 (ID-1). CONCLUSIONS. GST-based metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some helix-loop-helix nuclear proteins could he potentially important in organ-confined prostate cancer and deserve further investigation. Prostate 47:132-140, 2001. (C) 2001 Wiley-Liss, Inc.