A panel of eight-miRNA signature as a potential biomarker for predicting survival in bladder cancer

Abstract

BackgroundThere is increasing evidence to suggest that miRNAs play an important role in predicting cancer survival. To identify a panel of miRNA signature that can divided tumor from normal bladder using miRNA expression levels, and to assess the prognostic value of this specific miRNA markers in bladder cancer (BCa).MethodsA comprehensive meta-review of published miRNA expression profiles that compared BCa and adjacent normal tissues was performed to determine candidate miRNAs as prognostic biomarkers for BCa. Vote-counting strategy and Robust Rank Aggregation method were used to identify significant meta-signature miRNAs.ResultsWe identified an eight-miRNA signature including three upregulated (miR-141, miR-200c, miR-21) and five downregulated (miR-145, miR-125, miR-199a, let-7c and miR-99a) miRNAs for the prediction of overall survival (OS) using TCGA dataset, and validated in our 48 BCa patients. X-tile plot was used to generate the optimum cut-off point and Kaplan-Meier method was used to calculate OS. A linear prognostic model of eight miRNAs was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group were associated with poor OS compared with patients in the low-risk group (HR = 5.21, p < 0.001). Our validation cohort of 48 patients confirmed the panel of 8-miRNAs as a reliable prognostic tool for OS in patients with BCa (HR = 5.04, p < 0.001).ConclusionThe present meta-analysis identified eight highly significant and consistently dysregulated miRNAs from 19 datasets. We also constructed an eight-miRNA signature which provided predictive and prognostic value that complements traditional clinicopathological risk factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0167-0) contains supplementary material, which is available to authorized users.

Low expression of miR-1469 predicts disease progression and unfavorable post-surgical clinical outcomes in patients with esophageal squamous cell cancer

“…The small nuclear RNA U6, which is highly conserved and universally expressed, was used as the endogenous reference. Relative changes of miR-1469 expression were calculated using the comparative threshold cycle (2 -ΔΔCq ) method (18) and normalized to U6 expression. All RT-qPCR reactions were performed in triplicate.…”

Both cancerous miR‐21 and stromal miR‐21 in urothelial carcinoma are related to tumour progression

“…Bladder cancer shows up‐regulation of miR‐21, and high miR‐21 levels are related to a poorer prognosis of bladder cancer . Cancer of the upper urinary tract also shows increased miR‐21 levels .…”

Comprehensive investigation of aberrant microRNA profiling in bladder cancer tissues

“…They identified an eight-miRNA signature, including three up-regulated (miR-141, miR-200c, and miR-21) and five down-regulated (miR-145, miR-125, miR-199a, let-7c, and miR-99a) miRNAs for the prediction of overall survival (OS) using TCGA dataset, and further validated in 48 bladder cancer patients. However, Zhou et al focused on the prognostic value of these specific miRNA markers in bladder cancer [17], distinct from the current study which emphasized the different expression pattern of miRNA profiling between bladder cancer and noncancerous bladder tissues.…”

“…Moreover, miR-99a-5p was also decreased in plasma and urine supernatants of bladder cancer patients [24,26,27]. Besides the diagnostic value, miR99a-5p was a predictive marker of OS of bladder cancer by both of studies based on clinical samples and TCGA resource [17,28]. Meanwhile, enforced expression of miR-99a-5p could inhibit the cell proliferation, migration, and invasion of bladder cancer cells [26,29] and miR99a-5p is likely to directly target fibroblast growth factor receptor 3 in bladder cancer [29].…”

“…Zhou et al performed a meta-review of published miRNA expression profiles to designate candidate miRNAs as prognostic biomarkers for bladder cancer [17]. They identified an eight-miRNA signature, including three up-regulated (miR-141, miR-200c, and miR-21) and five down-regulated (miR-145, miR-125, miR-199a, let-7c, and miR-99a) miRNAs for the prediction of overall survival (OS) using TCGA dataset, and further validated in 48 bladder cancer patients.…”