Four biomarkers have been identified that correctly determine the malignancy of urinary bladder cancers and contribute to accurate predictions of patient outcomes.
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. By focusing on the role of microRNAs (miRNAs), which are small noncoding 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 of the miRNAs correlated with overall survival time.
Urinary bladder cancer is the fourth most common cancer in the West. The National Cancer Institute estimates 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, 75% of patients have cancers that 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 published in The Journal of Molecular Diagnostics (2013; 15(5):695-705), 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 with healthy tissue. Four miRNAs were expressed differently in bladder cancers that invaded muscle compared with 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,” said lead investigator Klaus Jung, MD, of the Department of Urology at the University Hospital Charité, Berlin and the Berlin Institute for Urologic Research in Germany.
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. Also, 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,” said 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.”