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Genes 2017, 8(2), 77; doi:10.3390/genes8020077

MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype

Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
Department of Urology, Hospital de Clinicas de Porto Alegre, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil
Cell and Molecular Biology Laboratory, Lahey Hospital and Medical Center, Burlington, MA 01805, USA
Biostatistics Research, Institute for Clinical Research Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA
Department of Pathology, University of Wisconsin, Madison, WI 53726, USA
These authors contributed equally to this work and are listed in alphabetical order.
Author to whom correspondence should be addressed.
Academic Editors: J. Peter W. Young and George A. Calin
Received: 28 September 2016 / Revised: 10 January 2017 / Accepted: 11 February 2017 / Published: 17 February 2017
(This article belongs to the Special Issue microRNAs and Other Non-Coding RNAs in Human Diseases)
View Full-Text   |   Download PDF [2104 KB, uploaded 17 February 2017]   |  


The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3–T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease. View Full-Text
Keywords: microRNA; non-muscle invasive bladder cancer; progression; intravesical therapy microRNA; non-muscle invasive bladder cancer; progression; intravesical therapy

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lenherr, S.M.; Tsai, S.; Silva Neto, B.; Sullivan, T.B.; Cimmino, C.B.; Logvinenko, T.; Gee, J.; Huang, W.; Libertino, J.A.; Summerhayes, I.C.; Rieger-Christ, K.M. MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype. Genes 2017, 8, 77.

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