Expression profiling for bladder cancer: strategies to uncover prognostic factors

Abstract

Despite being a common cancer worldwide, management of transitional cell carcinoma of the bladder currently relies primarily on clinical staging and histopathologic parameters. Assaying alterations in molecular pathways can contribute valuable information that can accurately predict outcome and chemotherapeutic response in individual patients with bladder cancer. Medium- to high-throughput gene-expression profiling technologies are now allowing multiplexed assessment of alterations responsible for the genesis and progression of bladder tumors. These investigations employ global or pathway-based approaches to define molecular signatures that can predict prognosis independent of traditional clinical performance metrics. Prognostic panels generated using these strategies can also elucidate the biology of tumor progression and identify potential therapeutic targets.

Figure 1. Subjective evaluation of the clinical utility of marker panels identified in different bladder cancer expression-profiling studies

Studies have been identified by the last name of the first author and corresponding reference number on the horizontal axis. The major marker panel identified in each study has been classified by its primary clinical output (diagnostic/prognostic/therapeutic; purple circles corresponding to the shaded blue regions labeled on the left) and feature size (triangles corresponding to right vertical axis). Both metrics in combination influence the potential clinical utility of each signature.

Figure 2. Examples of pathway-specific markers investigated in bladder cancer

Mitra et al. [34,36] and Birkhahn et al. [32] have profiled genes across several broad pathways commonly deregulated in cancer on primary bladder tumors to develop molecular panels for detection of adverse events. The primary effector pathways of tumorigenesis include apoptosis, cell cycle, gene regulation, cell growth regulation and antioxidation. There is considerable overlap of markers among the first three pathways. pathways include signal transduction, angiogenesis and invasion. Modified with permission from [34].