An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer

Abstract

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).Conclusion: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.

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer

“…Reports on bladder cancer-specific miRNA signatures in urine samples are rare (12,15,16,(26)(27)(28). Using the RT-qPCR-based microarray we investigated the abundance of 754 different human miRNA species.…”

“…In bladder cancer, urinary miR-126 was described as a specific indicator of BC (16), while overexpressed miR-96 and miR-183 were found to be correlated to tumour stage and grade (15). Another study showed a characteristic panel of 3 miRNAs (miR-15b/ miR-135b/miR-1224-3p) in urine sediments for detecting urothelial cell carcinomas (12).…”

“…miRNAs in easily accessible body fluids could reflect tissue situation and are therefore of great, diagnostic and prognostic interest. Data regarding the detection of miRNAs in urine samples have been rarely published (12)(13)(14)(15)(16). In bladder cancer, urinary miR-126 was described as a specific indicator of BC (16), while overexpressed miR-96 and miR-183 were found to be correlated to tumour stage and grade (15).…”

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

“…However, this study admitted missing 3% of invasive cancers using microRNAs (n=2). [32] Molecular markers as a predictor of tumor recurrence Using fluorescent-labeled DNA segments to detect chromosomal abnormalities associated with urothelial cancer is known as fluorescence in-situ hybridization (FISH). FISH has been shown to be 79% sensitive and 70% specific for diagnosing urothelial cancer.…”

Highly sensitive and specific novel biomarkers for the diagnosis of transitional bladder carcinoma

“…BCa exhibits significant tumor heterogeneity, reflected by multiple genetic alterations and complex somatic mutational profiles [2]. New biomarkers, based on DNA methylation profiling [3], point mutations [4] and microRNAs [5], have been established in addition to many proposed protein biomarkers.…”