A MicroRNA expression profile defining the invasive bladder tumor phenotype.
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.
Wszolek
Matthew F
MF
Department of Urology, Lahey Clinic Medical Center, Burlington, MA 01805, USA.
Rieger-Christ
Kimberly M
KM
Kenney
Patrick A
PA
Gould
Justin J
JJ
Silva Neto
Brasil
B
Lavoie
Amanda K
AK
Logvinenko
Tanya
T
Libertino
John A
JA
Summerhayes
Ian C
IC
D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D035683:MicroRNAs