MicroRNAs Have Diagnostic and Prognostic Potential in Urinary Bladder Cancer
Two miRNAs found to correlate with survival, say researchers
in The Journal of Molecular Diagnostics
Two miRNAs found to correlate with survival, say researchers in The Journal of Molecular Diagnostics
German researchers have identified four biomarkers that correctly determine malignancy of urinary bladder cancers and contribute to the accurate prediction of patient outcomes. Their results are published in the September issue of The Journal of
Current prognosticators of bladder cancer, such as tumor grade, stage, size, and number of foci, have limited usefulness for clinicians since they do not accurately reflect clinical outcomes. Therefore, investigators have been searching for new biomarkers with better diagnostic and prognostic capabilities. Focusing on the role of microRNAs (miRNAs), small non-coding RNAs, researchers have identified four miRNAs that together perfectly discriminated between nonmalignant and malignant tissue, including one alone that classified 81% of the samples correctly. Levels of two miRNAs correlated with overall survival time.
Urinary bladder cancer is the fourth most common cancer in the West. According to the National Cancer Institute, it is estimated that in the United States 72,570 individuals will be diagnosed with and 15,210 will die of cancer of the urinary bladder in 2013. At presentation, in 75% of patients the cancers are confined to the mucosa or submucosa (known as non-muscle invasive bladder cancer, NMIBC), whereas in 25% of cases the cancers have already invaded nearby muscle (muscle-invasive bladder cancer, MIBC).
In a series of experiments, investigators analyzed bladder tissue from patients with NMIBC, MIBC, and nonmalignant bladders. After screening 723 miRNAs by microarray, they selected a subset of 15 distinctively deregulated miRNAs for further validation by real-time quantitative PCR. Seven miRNAs were found to be up-regulated, and eight were down-regulated in malignant bladder tissue samples compared to healthy tissue. Four miRNAs were expressed differently in bladder cancers that invaded muscle compared to those that did not. With one exception, no correlation was found between tumor stage and miRNA levels.
When all 15 of the selected miRNAs were considered together, they correctly classified 100% of tissues as either normal or malignant. Further analysis identified four miRNAs that led to 100% correct classification, and one miRNA (miR-130b) that by itself had an 81% accuracy rate. "These results underline the great potential of miRNAs to serve as diagnostic markers, as previously noted for other urological tumors," says lead investigator Klaus Jung, MD, the Department of Urology at the University Hospital Charité, Berlin and the Berlin Institute for Urologic Research.
The investigators found that tumor grading could not be correlated with overall survival. Yet, they were able to find two miRNAs that significantly correlated with survival: miR-141 and miR-205. miR-141 showed a trend (P=0.08) of being able to stratify patients with muscle-invasive tumors into two groups with different overall survival times. "This finding could be of clinical importance, but these results must be interpreted cautiously," says Dr. Jung. "However, previously published studies underline the possible prognostic potential of miRNAs to predict progression and disease-specific or overall survival in bladder cancer patients."
miRNAs are small non-coding RNAs that contain between 19 and 24 nucleotides. miRNAs regulate gene expression by degrading messenger RNAs or impairing their translation. In recent years there has been a growing interest in miRNAs as potential diagnostic and/or prognostic biomarkers in cancers and other diseases.
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Notes for Editors
"MicroRNA Profiling Identifies Candidate miRNAs for Bladder Cancer Diagnosis and Clinical Outcome," by Nadine Ratert, Hellmuth-Alexander Meyer, Monika Jung, Poline Lioudmer, Hans- Joachim Mollenkopf, Ina Wagner, Kurt Miller, Ergin Kilic, Andreas Erbersdobler, Steffen Weikert, and Klaus Jung, DOI: http://dx.doi.org/10.1016/j.jmoldx.2013.05.008. The Journal of Molecular Diagnostics, Volume 15, Issue 5 (September 2013) published by Elsevier.
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About The Journal of Molecular Diagnostics
The Journal of Molecular Diagnostics, (http://jmd.amjpathol.org), the official publication of the Association for Molecular Pathology, co-published by the American Society for Investigative Pathology, seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome for review articles that contain: novel discoveries or clinicopathologic correlations including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods for diagnosis or monitoring of disease or disease predisposition.
The Journal of Molecular Diagnostics, with an Impact Factor of 3.952, ranks 15th among 77 journals in Pathology, according to 2012 Journal Citation Reports® Thomson Reuters, 2013.
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