Genome‐wide identification of urinary cell‐free microRNAs for non‐invasive detection of bladder cancer

Abstract

Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non‐invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT‐PCR. Whole‐genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR‐31‐5p, miR‐93‐5p and miR‐191‐5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2‐miRNA‐based urinary DxScore (miR‐93‐5p, miR‐31‐5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post‐operatively. In conclusion, we identified and independently validated cell‐free urinary miRNAs as promising biomarkers enabling non‐invasive detection of BCA.

Circulating miRNA panels for specific and early detection in bladder cancer

“…Recently, the molecular characterization of cell‐free DNA, circulating tumor DNA and circulating miRNA by liquid biopsy is an attractive alternative to tissue biopsy to diagnose cancer and other diseases . For diagnosis of bladder cancer by liquid biopsy, there are several reports of biomarker searches with large samples, including those detecting tumor‐specific hotspot mutations in serum DNA or miRNA in urine from patients .…”

“…19 Notably, the 7-miRNA panel in bladder cancer is also effective for the detection of both low and high grades (92.7% and 96.1% in sensitivity, respectively), Recently, the molecular characterization of cell-free DNA, circulating tumor DNA and circulating miRNA by liquid biopsy is an attractive alternative to tissue biopsy to diagnose cancer and other diseases. [13][14][15][20][21][22][23] In addition, urinary cytology, which has high specificity but low sensitivity, is commonly used for detecting bladder cancer. In the bladder cancer group, many cases also had not been captured by urinary cytology (Table 1).…”

“…MicroRNA (miRNA) are small non-coding RNA made up of [18][19][20][21][22][23][24] base pairs with single chain molecules. 5,6 MiRNA modulate gene expression by decreasing target mRNA stability or repressing translational efficiency.…”

Molecular mechanism and role of microRNA‐93 in human cancers: A study based on bioinformatics analysis, meta‐analysis, and quantitative polymerase chain reaction validation

“…Separately, 11 studies from eight articles 15,[56][57][58][59][60][61][62] were included in the diagnostic meta-analysis and 14 studies from 13 articles 15,24,29,41,47,51,[63][64][65][66][67][68][69] were included in the prognostic meta-analysis. After screening the titles and abstracts, 476 articles were excluded because they were reviews (n = 18), meta-analyses (n = 5), nonhuman studies (n = 14), or studies irrelevant to our topic (n = 439).…”

Current Methods of microRNA Analysis

“…Značná variabilita může být rovněž dána použitou metodou analýzy či subjektivní chybou při vyhodnocování dat a vylučováním odlehlých hodnot. Úspěšným příkladem je patentovaný dia gnostický test pro detekci hladin miR-31-5p, miR-93-5p a miR-191-5p v močovém supernatantu, kterým lze odlišit pacienty s karcinomem močového měchýře od zdravých jedinců [30].…”