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Introduction: MicroRNAs (miRNAs) are small, non-coding segments of regulatory RNA that have emerged as powerful biomarkers of disease severity and prognosis. We previously reported a miRNA profile (miR-200c, miR-141, and miR-30b) capable of differentiating invasive from noninvasive urothelial carcinoma of the bladder (UCB) with a sensitivity of 100% and a specificity of 96%. The goal of this project is to validate this profile with an expanded sample pool that includes tissues from an independent institution.
Materials & Methods: MiRNA expression levels in tumor tissue and cell lines were quantified by qRT-PCR. Fifty UCB cell lines and 157 UCB tumors (76 noninvasive and 81 invasive) were evaluated. Downstream targets were assessed via Western blot analysis.
Results: On multi-institutional analysis, the original miRNA panel remained capable of distinguishing between invasive and non-invasive UCB, however, the sensitivity and specificity were both reduced to 82%. To address this we identified additional miRNAs that were correlated with invasive potential in a screen of 50 cell lines. When evaluated in tumor samples from both institutions, several of these additional miRNAs were significantly different between invasive and non-invasive tumors.
Conclusions: Multi-institutional analysis of our panel of miRNAs capable of defining the invasive bladder tumor phenotype was confirmed albeit with a slightly reduced sensitivity and specificity. Expansion of miRNA analysis in UCB cell lines resulted in the identification of additional miRNAs with differentiating potential, several of which were found to significantly discriminate invasive from non-invasive tumors. Improvements in specificity and sensitivity with these additional miRNAs will be evaluated.