Circulating miRNAs Act as Diagnostic Biomarkers for Bladder Cancer in Urine

Abstract

MicroRNAs (miRNAs) can be secreted into body fluids and have thus been reported as a new type of cancer biomarker. This study aimed to determine whether urinary miRNAs act as noninvasive biomarkers for diagnosing bladder cancer. Small RNA profiles from urine were generated for 10 patients with bladder cancer and 10 healthy controls by using next-generation sequencing. We identified 50 urinary miRNAs that were differentially expressed in bladder cancer compared with controls, comprising 44 upregulated and six downregulated miRNAs. Pathway enrichment analysis revealed that the biological role of these differentially expressed miRNAs might be involved in cancer-associated signaling pathways. Further analysis of the public database revealed that let-7b-5p, miR-149-5p, miR-146a-5p, miR-193a-5p, and miR-423-5p were significantly increased in bladder cancer compared with corresponding adjacent normal tissues. Furthermore, high miR-149-5p and miR-193a-5p expression was significantly correlated with poor overall survival in patients with bladder cancer. The qRT-PCR approach revealed that the expression levels of let-7b-5p, miR-149-5p, miR-146a-5p and miR-423-5p were significantly increased in the urine of patients with bladder cancer compared with those of controls. Although our results indicated that urinary miRNAs are promising biomarkers for diagnosing bladder cancer, this must be validated in larger cohorts in the future.

Impacts of mir146a genotypes to bladder cancer risk in Taiwan

“…In the current study, the signi cantly higher expression levels for people carrying the variant genotypes (CG and GG) of mir146a rs2910164 than those carrying the wile-type CC genotypes provide biological plausibility for the associations of CG and GG genotypes with increased BLCA risks. The ndings are in line with that of Lin and Tsai's previous reports, mentioning that mir146a were signi cantly elevated in the urine of BLCA patients than the normal controls 24 . Although the pilot study is of relatively small sample size, the elevation of mir146a has been also con rmed in The Cancer Genome Atlas database with 19 controls and 416 BLCA cases.…”

“…While one came out with negative ndings 22 , the other provided evidence that mir146a rs2910164 may play an important role in BLCA 23 . More recently, Lin and Tsai reported mir196a, in addition to mir146a, was signi cantly increased in its expression level among BLCA patients 24 .…”

miRNAs in the Era of Personalized Medicine: From Biomarkers to Therapeutics

“…In particular, the loss of endothelial miR-126 might explain the impaired peripheral angiogenic signaling in patients [ 23 ]. In the current special issue, outstanding examples have been provided by Lin and Tsai [ 24 ] and Oto et al [ 25 ] in bladder and renal cell cancer, respectively, and by Salloum-Asfar et al in Autism Spectrum Disorder [ 26 ].…”

Diagnostic Potential of Circulating Tumor Cells, Urinary MicroRNA, and Urinary Cell-Free DNA for Bladder Cancer: A Review

“…Use of NGS to analyze umiRNAs has another advantage, in that researchers can verify their data by referring to published databases such as The Cancer Genome Atlas (TCGA), which generates and analyzes NGS data from the whole genome in various cancer types. Two recent studies explored expression levels of umiRNAs in patients with BCa and, using data from TCGA, validated an overlapping of certain miRNAs with altered expression levels [ 44 , 45 ]. Braicu et al identified five umiRNAs in common between a patient cohort and TCGA data [ 44 ].…”