MicroRNA Profiling Shows Promise as Diagnostic and Prognostic Tool for Bladder Cancer

By LabMedica International staff writers
Posted on 28 Aug 2013

Profiling of 15 microRNAs (miRNAs) from bladder tissue showed with 100% accuracy whether the cells were normal or malignant, while the determination of only two miRNAs could predict how well the patient would be able to defend against bladder cancer.

Bladder cancer is a common cancer in the Western world. However, the current prognosticators such as tumor grade, stage, size, and multifocality do not accurately reflect the clinical outcome. In about three-quarters of bladder cancer patients the tumors are confined to the mucosa or submucosa (non-muscle invasive bladder cancer, NMIBC), whereas in the rest of the cases the cancers have already invaded nearby muscle (muscle-invasive bladder cancer, MIBC).

Image: RNA microarray analysis: heat maps of gene expression values show how experimental conditions influenced production (expression) of miRNA for a set of genes. Green indicates reduced expression. Cluster analysis has placed a group of down regulated genes in the upper left corner (Photo courtesy of Wikimedia Commons).

Investigators at University Hospital Charité (Berlin, Germany) turned to the profiling of microRNAs from bladder tissue as a better way to detect cancer and predict how it would likely grow and spread. MicroRNAs are snippets of about 20 nucleotides that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA.

The investigators screened 723 miRNAs by microarray and selected a subset of 15 distinctively deregulated miRNAs for further validation by real-time quantitative RT-(q)PCR. Seven miRNAs were found to be up-regulated and eight miRNAs were found to be down-regulated in malignant bladder tissue samples compared to healthy tissue. Four miRNAs that had already been described in the literature (miR-141, miR-199a-3p, miR-205, and miR-214) were significantly differentially expressed between non-muscle-invasive and muscle-invasive bladder cancer.

When all 15 of the selected miRNAs were considered together, they correctly classified 100% of tissues as either normal or malignant, and two miRNAs (miR-141 and miR-205) significantly correlated with survival.

"These results underline the great potential of miRNAs to serve as diagnostic markers, as previously noted for other urological tumors," said senior author Dr. Klaus Jung, professor of urology at the University Hospital Charité. "These findings could be of clinical importance, but these results must be interpreted cautiously. However, previously published studies underline the possible prognostic potential of miRNAs to predict progression and disease-specific or overall survival in bladder cancer patients."

The study demonstrating the usefulness of miRNA profiling for diagnosis and prognosis of bladder cancer was published in the August 14, 2013, online edition of the Journal of Molecular Diagnostics.

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University Hospital Charité