1270 Micrornas Detection in Urine as Diagnostic Markers and Predictors of Recurrence of Non-Muscle Invasive Bladder Cancer

You have accessJournal of UrologyBladder Cancer: Detection and Screening1 Apr 20121270 MICRORNAS DETECTION IN URINE AS DIAGNOSTIC MARKERS AND PREDICTORS OF RECURRENCE OF NON-MUSCLE INVASIVE BLADDER CANCER Hideki Enokida, Yasutoshi Yamada, Hirofumi Yoshino, Shuichi Tatarano, Hideo Hidaka, Takeshi Yamasaki, Takeshi Chiyomaru, Satoko Kojima, Naohiko Seki, and Masayuki Nakagawa Hideki EnokidaHideki Enokida Kagoshima, Japan More articles by this author , Yasutoshi YamadaYasutoshi Yamada Kagoshima, Japan More articles by this author , Hirofumi YoshinoHirofumi Yoshino Kagoshima, Japan More articles by this author , Shuichi TataranoShuichi Tatarano Kagoshima, Japan More articles by this author , Hideo HidakaHideo Hidaka Kagoshima, Japan More articles by this author , Takeshi YamasakiTakeshi Yamasaki Kagoshima, Japan More articles by this author , Takeshi ChiyomaruTakeshi Chiyomaru Kagoshima, Japan More articles by this author , Satoko KojimaSatoko Kojima Ichihara, Japan More articles by this author , Naohiko SekiNaohiko Seki Chiba, Japan More articles by this author , and Masayuki NakagawaMasayuki Nakagawa Kagoshima, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1602AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Currently, tumor marker for bladder cancer (BC) depends on urine cytology because of its high specificity (around 95%) despite of its low sensitivity (around 30%). MicroRNAs (miRNAs) are small noncoding RNAs of about 22 nucleotides in length and function as negative regulators of gene expression and are aberrantly expressed in various human malignancies. Our previous miRNA screening of BC demonstrated that miR-96 and miR-183 were the top two up-regulated miRNAs among 667 miRNAs. We hypothesize that these miRNAs are detectable in urine and useful biomarkers for predicting recurrence of non-muscle invasive BC as well as diagnosing BC. METHODS Total RNA of urine was extracted from 85 BCs, 25 urinary tract infections (UTIs) and 49 healthy controls (HCs). A real-time PCR based experiment was used to evaluate expression levels of the miRNAs. On the basis of absolute quantification method, the expression level of each miRNA was calculated by a following formula: expression level = 2(40-Ct). RESULTS The expression levels of miR-96 and miR-183 in urine from BCs were significantly higher than that from UTIs or HCs (P<0.0001). ROC curve analysis revealed that miR-96 and miR-183 have good sensitivity (71.0 and 74.0%) and specificity (89.2 and 77.3%) to distinguish BC from non-BC patient. We found significant difference in miR-96 and miR-183 expressions between invasive (> pT1) and non-invasive (pTa) UCs (each, P<0.05), and there were positive correlations between their expression and tumor grade (each, P<0.01). To our surprise, miR-96 was positively detected in 27 of 44 BC patients who had a negative diagnosis by urine cytology. When we combined miRNA analysis with urine cytology in our cohort, the sensitivity reached to 78.2% for BC detection. Kaplan-Meyer analysis revealed negative expression of miR-183 was associated with recurrence-free survival in patients with non-muscle invasive bladder cancer (P=0.0441). CONCLUSIONS Our data suggest that detection of miR-96 and miR-183 may serve as potential biomarkers for BC diagnosis as well as prediction for tumor recurrence of non-muscle invasive BC. ROC curve analysis of urine samples: distinguishing BC from non-BC patients miRNA AUC S.E 95% C.I. Cut-off Sensitivity (%) Specificity (%) miR-96 0.831 0.030 0.767-0.884 284 71.0 89.2 miR-183 0.817 0.031 0.752-0.872 466 74.0 77.3 © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e514 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hideki Enokida Kagoshima, Japan More articles by this author Yasutoshi Yamada Kagoshima, Japan More articles by this author Hirofumi Yoshino Kagoshima, Japan More articles by this author Shuichi Tatarano Kagoshima, Japan More articles by this author Hideo Hidaka Kagoshima, Japan More articles by this author Takeshi Yamasaki Kagoshima, Japan More articles by this author Takeshi Chiyomaru Kagoshima, Japan More articles by this author Satoko Kojima Ichihara, Japan More articles by this author Naohiko Seki Chiba, Japan More articles by this author Masayuki Nakagawa Kagoshima, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...