MicroRNA expression profiling in bladder cancer: the challenge of next-generation sequencing in tissues and biofluids

Bladder cancer (BC) is a heterogeneous disease characterized by a high recurrence rate that necessitates continuous cystoscopic surveillance. MicroRNAs (miRNAs) are detectable in tissues and biofluids such as plasma/serum and urine. They represent promising biomarkers with potential not only for detecting BC but also informing on prognosis and monitoring treatment response. In this review, the many aspects of the application of next-generation sequencing (NGS) to evaluate miRNA expression in BC is discussed, including technical issues as well as a comparison with results obtained by qRT-PCR. The available studies investigating miRNA profiling in BC by NGS are described, with particular attention to the potential applicability on biofluids. Altered miRNA levels have been observed in BC tissues by NGS, but these results so far only partially overlapped among studies and with previous data obtained by qRT-PCR. The discrepancies can be ascribed to the small groups of BC patients sequenced. The few available studies on biofluids are mainly focused on implementing RNA isolation and sequencing workflow. Using NGS to analyze miRNAs in biofluids can potentially provide results comparable to tissues with no invasive procedures for the patients. In particular, the analyses performed on exosomes/microvesicles appear to be more informative. Thanks to the improvement of both wet-lab procedures and pipelines/tools for data analyses, NGS studies on biofluids will be performed on a larger scale. MiRNAs detected in urine and serum/plasma will demonstrate their potentiality to describe the variegated scenario of BC and to become relevant clinical markers.