Using microRNA (miRNA) profiling to differentiate noninvasive and muscle-invasive from metastases of transitional cell carcinoma of the urinary bladder (TCC-UB).

Abstract

338 Background: Altered miRNA expression contributes to the pathogenesis of urologic malignancies, including bladder cancer (BC). Individual miRNAs are known to regulate multiple signaling pathways in BC. We hypothesized that identifying miRNA gene expression profiles (GEP) in TCC-UB in the localized (non-invasive Vs invasive) and metastatic setting will help identify predictive and prognostic biomarkers within oncogenic signaling pathways, and novel therapeutic targets. Methods: We conducted a retrospective review of pathology reports of patients with TCC-UB from 2005 - 2013. The samples were categorized into non-invasive, muscle-invasive and metastatic sites. Normal urothelium was used as controls. Bone metastasis and tumors with squamous differentiation were excluded. RNA was extracted from Formalin Fixed Paraffin Embedded (FFPE) tissue blocks and assessed with Nanostring - nCounter miRNA expression assays. The Student t test was used to analyze the data. P value of < 0.05 was considered statistically significant. Results: 36 FFPE tumor samples were identified and analyzed – 18 muscle-invasive (MI), 9 non-invasive (NI), 7 metastatic (M) and 2 normal urothelium (C). Of the over 600 miRNA assessed by the Nanostring microarray, miR21 and 494 were consistently up-regulated, while miR451a, 144-3p, 363-3p, 15b-5p, 200a-3p, 137, 429 were downregulated. Conclusions: MicroRNA profiling differentiates non-muscle invasive versus muscle-invasive BC from metastatic sites. The data provides insights into molecular alterations that will help distinguish signaling pathways of bladder carcinogenesis such as FGFR, PI-3K, STAT-3 and p53. Identified molecular targets will provide an effective and promising strategy to be evaluated in BC cell lines. [Table: see text]