Use of High-Throughput DNA Microarrays to Identify Biomarkers for Bladder Cancer

Abstract

Background: Numerous markers have been described to correlate to some extent with tumor stage and prognosis of patients with bladder cancer. The power of many of these biomarkers in detecting superficial disease or predicting the clinical outcome of individual tumors is limited, and alternative markers are still in demand. High-throughput microarrays represent novel means for cancer research and tumor marker discovery. Approach: The aim of this report was to discuss the application of DNA technologies to provide novel biomarkers for bladder cancer. Content: Specific bladder tumor subtypes have distinct gene expression profiles. The use of high-throughput DNA microarrays allows identification of the most prevalent and relevant alterations within bladder tumors. Clusters of differentially expressed genes will become biomarkers to discriminate subgroups of patients with different histopathology or clinical outcome. Additionally, the identified individual molecular targets might be further validated and developed into novel serum or urinary biomarkers for the diagnosis and/or as prognostic factors to be applied in clinical practice. The diagnosis and prognosis of bladder cancer would be enhanced by the use of such markers, and the marker itself may constitute a therapeutic target when studied in appropriate patients and control groups. Summary: Expression profiling with high-throughput DNA microarrays has the potential of providing critical clues for the management of bladder cancer patients. As the quality, standardization, and ease of use of the technology increase and the costs decrease, DNA microarrays will move from being a technology restricted to research to clinical laboratories in the near future.

Bladder Cancer Outcome and Subtype Classification by Gene Expression

“…Hierarchical clustering separated tumors into two clearly distinct groups, superficial and muscle invasive, similar to previous reports (12,13,16,17). When a set of nine bladder tumor cell lines was included in the unsupervised clustering, eight of nine (all derived from advanced tumors) were grouped in a separate subcluster with five muscle-invasive tumors.…”

“…In bladder cancer, expression patterns have identified gene signatures that are associated with tumor stage (16,17) and superficial recurrence (16). However, the number of muscle-invasive tumors reported in those studies was small, and robust outcome classification models for the invasive tumors were not possible.…”

“…To date, the number of published studies on bladder cancer using microarray expression profiling has been rather limited and only a few publications have involved clinical material (12,15,16). These studies have identified gene signatures that were associated with tumor stage (16,17) and superficial recurrence (16). However, the number of muscle-invasive tumors reported in these studies is small, and robust outcome classification models for the invasive tumors were not feasible.…”

Thymidine kinase 1: A proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients

“…MUC1 levels are high in advanced disease and serum MUC1 levels may be useful in monitoring disease, (11). It is suggested that high-throughput DNA micro-arrays will soon move from being technology restricted to research and clinical laboratories (12). Methylation of the p16 (INK4a) promoter may be a new type of tumor marker in bladder cancer (13).…”

Hybridization Isotherms of DNA Microarrays and the Quantification of Mutation Studies

“…In turn, the mutated DNA can provide diagnostically useful molecular markers (2 ). Among them are point mutations, which involve a change in a single base pair in the DNA, such as those occurring in the p53 and K-ras genes (3)(4)(5). The detection of such point mutations is useful in screening for cancers (6 ) as well as for typing of cancers to optimize treatment protocols (7 ).…”