Gene expression profiling in bladder cancer to identify potential therapeutic targets.

Abstract

4518 Background: Characterization of gene expression patterns in bladder cancer (BC) allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Methods: Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Results: Hierarchical clustering defined signatures, which differentiated between cancer and normal, muscle-invasive or non-muscle invasive cancer and normal, g1 and g3. Pathways associated with cell cycle and proliferations were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer as compared to normal tissue. Conclusions: This study contributes to a growing body of work on gene expression signatures in BC. The data support an important role for osteopontin in BC, and identify several pathways worthy of further investigation. [Table: see text]