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A MicroRNA expression profile defining the invasive bladder tumor phenotype

Authors :
Amanda K. LaVoie
Matthew F. Wszolek
Ian C. Summerhayes
Tanya Logvinenko
Patrick A. Kenney
Kimberly M. Rieger-Christ
Brasil Silva Neto
John A. Libertino
Justin J. Gould
Source :
Urologic Oncology: Seminars and Original Investigations. 29:794-801.e1
Publication Year :
2011
Publisher :
Elsevier BV, 2011.

Abstract

Objective The purpose of this study was to identify microRNA (miRNA) involved in the transition between the noninvasive and invasive urothelial carcinoma of the bladder (UCB) phenotype. Methods Differential expression of miRNA was identified in a microarray format between noninvasive and invasive UCB cell lines and confirmed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) within this cell panel. Normalization of qRT-PCR with miR-222 was established from the microarray data and validated within a panel of 57 UCB tumors (26 noninvasive lesions (Ta/G1) and 31 invasive lesions (T2-T4). Pre-miR constructs were transfected into appropriate UCB cell lines to establish a change in invasive potential. Results Differential expression of miRNAs was identified from microarray analysis and included reduced expression associated with miR-30b, miR-31, miR-141, miR-200a, miR-200b, miR-200c, miR-205, miR-21 in invasive lesions and elevated miR-99a in noninvasive UCB lesions. Reduced invasion potential was recorded in UM-UC-3, following pre-miR transfection, in all UCB cell lines with the exception of UM-UC-3/miR-30b transfectants. Our results identify a panel of miRNA modulated and expressed in invasive UCB tumors and demonstrates a role for them in the invasive phenotype. Conclusions The diagnostic test, based on the three most discriminatory miRNAs in our panel (miR-200c, miR-141, and miR-30b), showed a sensitivity of 100% and a specificity of 96.2%. Such a panel of miRNAs has the potential to identify invasive bladder tumors misclassified in pathologic assessment of bladder biopsy specimens.

Details

ISSN :
10781439
Volume :
29
Database :
OpenAIRE
Journal :
Urologic Oncology: Seminars and Original Investigations
Accession number :
edsair.doi.dedup.....2033fe1d07bb3fc4af8605850234d97e