Abstract
Introduction and Objectives MicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). Individual miRNAs have been shown to modulate multiple signaling pathways that contribute to BC. To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. Methods To determine candidate miRNAs as prognostic biomarkers for dividing aggressive type of UCB, miRNA expression was profiled in patients' samples with an aggressive phenotype or nonaggressive phenotype using 3D-Gene miRNA labeling kit (Toray, Japan). To create a prognostic index model, we used the panel of 9-miRNA signature based on Cancer Genome Atlas (TCGA) data portal (TCGA Data Portal (https://tcgadata.nci.nih.gov/tcga/tcgaHome2.jsp)). miRNA expression data and corresponding clinical data, including outcome and staging information of 84 UCB patients, were obtained. The Kaplan-Meier and log-rank test were performed to quantify the survival functions in two groups. Results Deregulation of nine miRNAs (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-4324, hsa-miR-34b-5p, hsa-miR-29c-3p, hsa-miR-135a-3p, and hsa-miR-33b-3p) was determined in UCB patients with aggressive phenotype compared with nonaggressive subject. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. Of nine miRNAs, six were associated with high risk (hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-4324, hsa-miR-34b-5p, and hsa-miR-135a-3p) and three were shown to be protective (hsa-miR-145-5p, hsa-miR-29c-3p, and hsa-miR-33b-3p). Patients with the high-risk miRNA signature exhibited poorer OS than patients expressing the low-risk miRNA profile (HR = 7.05, p < 0.001). Conclusions The miRNA array identified nine dysregulated miRNAs from clinical samples. This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB.
Highlights
Introduction and ObjectivesMicroRNA expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB)
In order to find more sensitive biomarkers, we focused on 10 miRs with the highest alteration levels in the tissue of UCB patients (Figure 3)
MicroRNAs are currently discovered as a class of short noncoding RNA, which is known to regulate posttranscriptional gene expression level, by binding to homologically identical sequences, to the 3′-UTR of target miRNAs, thereby resulting in translational inhibition accompanied with miRNA degradation [29]
Summary
Introduction and ObjectivesMicroRNA (miRNA) expression is altered in urologic malignancies, including urothelial carcinoma of the bladder (UCB). To identify a panel of miRNA signature that can predict aggressive phenotype from normal nonaggressive counterpart using miRNA expression levels and to assess the prognostic value of this specific miRNA markers in patients with UCB. To validate the prognostic power of the nine-signature miRNAs using the TCGA dataset of bladder cancer, the survival status and tumor miRNA expression of all 84 TCGA UCB patients were ranked according to the prognostic score values. The miRNA array identified nine dysregulated miRNAs from clinical samples This panel of nine-miRNA signature provides predictive and prognostic value of patients with UCB. MiRNA-based detection tools for the purpose of precision medicine emerged as an effective option and may offer a curative potential in UCB therapy, either alone or in combination with other therapies Due to their well-established selectivity and specificity, miRNAs can represent a useful tool, both in diagnosis and therapy, in forging the path towards the achievement of precision medicine [2]. The aim of the present study was to focus on the possible role of miRNA dysregulation in UCB and discuss the potential of miRNAs as prognostic biomarkers
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