An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer.
BACKGROUND
Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease.


METHODS
We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR.


RESULTS
We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs-15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance).


CONCLUSIONS
The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed.
Academic Urology Unit, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
S
S
Miah
E
E
Dudziec
R M
RM
Drayton
A R
AR
Zlotta
S L
SL
Morgan
D J
DJ
Rosario
F C
FC
Hamdy
J W F
JW
Catto
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*; D055815:Young Adult
D014408:Biomarkers, Tumor; D035683:MicroRNAs