title: MiR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology.
abstract: A new diagnostic marker for urothelial carcinoma (UC) is needed to avoid painful cystoscopy during the initial diagnosis and follow-up period. However, the current urine markers are useless because of the low sensitivities and specificities for UC detection. MiR-96 and miR-183 were differentially upregulated microRNA in our previous microRNA screening for UC. The expression levels of miR-96 and miR-183 in the urine samples were significantly higher in 100 UC than in healthy controls (miR-96, P=0.0059; and miR-183, P=0.0044). The receiver-operating characteristic curve analyses demonstrated that each microRNA had good sensitivity and specificity for distinguishing UC patients from non-UC patients (miR-96, 71.0% and 89.2%; and miR-183, 74.0% and 77.3%). Our cohort included 78 UC patients who had undergone urinary cytology. MiR-96 was positively detected in 27 of 44 patients who had had a "negative" urinary cytology diagnosis. We combined the miR-96 detection data with the urinary cytology data, and diagnosed 61 of 78 cases as UC; sensitivity rose from 43.6% to 78.2%. We found significant stepwise increases in miR-96 and miR-183 expression with advancing tumor grade (miR-96, P=0.0057; and miR-183, P=0.0036) and pathological stage (miR-96, P=0.0332; and miR-183, P=0.0117). The expression levels of the microRNA were significantly lower in urine collected after surgery (miR-96, P=0.0241; and miR-183, P=0.0045). In conclusion, miR-96 and miR-183 in urine are promising tumor markers for UC. In particular, miR-96 may be a good diagnostic marker in combination with urinary cytology.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.forename: Kazumori
authors.initials: K
authors.lastname: Kawakami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tatarano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kawahara
authors.forename: Kenryu
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; C533449:MIRN183 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs