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Evaluation of Candidate Urinary microRNAs in Upper Tract Urothelial Carcinoma: A Prospective Multicenter Biomarker
Shuichi Tatarano1, Hideki Enokida1, Hiroyuki Nishiyama2
1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Kagoshima, Japan.
Objectives:
To evaluate the clinical associations of candidate urinary microRNAs (miRNAs) in patients with upper tract urothelial carcinoma (UTUC), including their ability to discriminate patients with UTUC from healthy controls and their associations with relapse-free survival (RFS).
Methods:
This prospective multicenter ancillary study of the JCOG1403 trial (JCOG1403A1 study) included 45 patients with UTUC and 16 healthy controls. Four candidate miRNAs (miR-130b, miR-182, miR-191, and miR-200a) were selected based on prior exploratory sequencing analysis. Urinary cell fractions were isolated by cell sorting, and miRNA expression was quantified by stem-loop RT-qPCR. The ability of urinary miRNAs to discriminate patients with UTUC from healthy controls, their associations with clinicopathological characteristics, and their associations with RFS were evaluated.
Results:
Among the candidate miRNAs, miR-191 and miR-200a showed significantly increased expression in patients with UTUC and demonstrated favorable discrimination between patients with UTUC and healthy controls. The combined miR-191/miR-200a model showed the highest discriminatory performance (area under the curve, 0.888). Urine cytology was positive in 33.3% of evaluable patients, whereas urinary miR-191 and miR-200a were detectable in 78.6% and 85.7% of patients with negative/suspicious cytology, respectively. Preoperative urinary miR-182 and miR-191 detectability was significantly associated with pathological tumor stage. In exploratory prognostic analyses, patients with detectable postoperative urinary miR-130b had significantly shorter RFS (log-rank p = 0.0455); however, the association was not statistically significant in multivariable Cox regression analysis (hazard ratio 2.76, 95% confidence interval 0.84-9.05, p = 0.094).
Conclusions:
Urinary miR-191 and miR-200a showed potential for discriminating patients with UTUC from healthy controls and may complement urine cytology, particularly in patients with negative/suspicious cytology. The association between postoperative urinary miR-130b detectability and RFS should be considered exploratory and requires further validation.
