MicroRNA Expression In Bladder Cancer: A Ratiometric Approach Identifies Invasive Potential

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 14 Jun 2008 - 6:00 PDT

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ORLANDO, FL (UroToday.com) - One third of recurring non-invasive bladder cancer will be invasive. To date, there is no way of identifying those patients who will have this clinical outcome. The goal of this study was to identify a microRNA (miRNA) signature in bladder cancer capable of differentiating non-invasive from invasive disease and to determine the prognostic value of such an expression profile.

Expression profiling of 343 miRNAs was performed in a microarray format using 2 non-invasive and 2 invasive bladder carcinoma cell lines. The differential expression of miRNAs was confirmed using a single molecule detection platform assay within a panel of 14 bladder carcinoma cell lines. Mir-21 and mir-205 expression levels were determined in 53 bladder tumors, (28 non-invasive and 25 invasive) and analyzed using a ratiometric approach. Sensitivity, specificity and a ROC curve were calculated to determine the discriminatory power of the mir-ratio to predict invasion. Knockdown and forced expression of miRNAs was performed to confirm their role in invasion.

Microarray analysis identified 9 miRNAs differentially expressed between non-invasive and invasive cell lines that were confirmed in the platform assay. In an extended cell panel, differential expression involving high mir-21 and low mir-205 expression levels were identified associated with invasive cells. Although expression levels of these miRNAs could not discriminate between non-invasive and invasive tumors, the ratio of mir-21:mir-205 displayed excellent discriminatory power. The analysis of this quotient in 53 bladder tumors, representing non-invasive and invasive bladder lesions, showed an area under the ROC curve of 0.89 with 100% sensitivity and 78% specificity using a cutoff = 1.79 to predict an invasive lesion. Of 6 non-invasive lesions displaying a high mir-21:mir-205 ratio, 5 progressed to invasive disease. Knockdown and forced expression of mir-21 modified the invasive behavior of bladder tumor cell lines in in vitro invasion assays.

The investigators had identified a novel miRNA signature that can be used to generate a mir-21:mir-205 ratiometric score differentiating between non-invasive and invasive lesions. In addition, 5 of 6 patients with non-invasive tumors displaying a high ratiometric score presented at a later time with invasive lesions. Alterations in the expression level of mir-21 in vitro modulated the invasive behavior of bladder tumor cells.

Presented by Brasil Silva Neto, MD, et al., at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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