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• W1996304340 abstract "You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2012446 RENAL CELL CARCINOMA MICRO-RNA A MOLECULAR DETERMINANT OF METASTASIS Michael Garcia-Roig, Kateryna Kiselora, Travis Yates, Soum Lokeshwar, Ezekiel Young, Vincent Bird, Murugesan Manoharan, and Vinita Lokeshwar Michael Garcia-RoigMichael Garcia-Roig Miami, FL More articles by this author , Kateryna KiseloraKateryna Kiselora Miami, FL More articles by this author , Travis YatesTravis Yates Miami, FL More articles by this author , Soum LokeshwarSoum Lokeshwar Miami, FL More articles by this author , Ezekiel YoungEzekiel Young Miami, FL More articles by this author , Vincent BirdVincent Bird Gainesville, FL More articles by this author , Murugesan ManoharanMurugesan Manoharan Miami, FL More articles by this author , and Vinita LokeshwarVinita Lokeshwar Miami, FL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.513AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Up to 25% of patients with renal cell carcinoma (RCC) present with metastasis at initial diagnosis. Molecular determinants of RCC growth & metastasis may be accurate prognostic markers for metastasis. miRNAs (miRs) are 22-nucleotide non-coding segments that regulate gene expression by degrading target mRNAs. Therefore, specific miRs are molecular determinants of tumor growth & metastasis. We examined expression of seven miRs in kidney tumor & normal specimens & correlated the expression with metastasis. METHODS RCC & normal kidney specimens were collected from 86 patients undergoing nephrectomy. miR enriched total RNA was successfully isolated from 46 RCC & 59 normal kidney tissues. Clinical data was collected including tumor histology (oncocytoma 6, chromophobe 4, papillary 6, clear cell 25, sarcoma 4, & collecting duct 1), stage (T1: 20; T2: 9; T3: 10; T4: 1), renal vein involvement (+: 5; −: 41), & lymph node positivity (+: 4; −: 41). At 14 months median follow-up, 6 patients were positive for metastasis. Microarray (Thermo Fisher Scientific 10.1) was performed on 30 samples to identify 554 miR targets. Seven miRs were chosen (mir-21, 150, 155, 142-3p, 142-5p, 192, & 194) based on the fold change in tumor samples. Their expression was quantified by quantitative PCR, & normalized to a housekeeping miR. Statistical analysis was performed using the Mann-Whiteny U-test & multivariate analysis. RESULTS Microarray analysis identified significant upregulation of 65 & down-regulation of 47 miRs in RCC tissues (p<0.05). When compared to normal kidney, RCC specimens demonstrated that miR-155 levels were up-regulated by 4-fold (0.67±0.87 vs 2.7±4.5; P=0.0003) & miR-194 levels were 6.5-fold downregulated (320±352 vs 49.1±74.6; P<0.0001). Similarly, miR-192 expression was downregulated by 5.5-fold in RCC specimens (P<0.0001). miR-142-3p & miR-142-5p levels significantly correlated with tumor grade; median levels in high-grade (3p: 52.97; 5p: 6.2) were 6.8-13.7-fold elevated when compared to low-grade tumors (3p: 7.8; p=0.028; chi-sq =4.8; 5p: 0.45; p=0.003; chi-sq: 8.7). In multivariate analysis which included TMN, renal vein, lymphovascular invasion, age, gender & miR levels, only mir-194 expression was associated with metastasis (p=0.034; chi-sq: 4.5). None of the miRs studied correlated with tumor size or lymphovascular invasion, but miR194 correlated with renal vein involvement (P=0.05). CONCLUSIONS miR-155, 192, 194, & 21 are differentially expressed in kidney cancer. While miR-142 (3p, 5p) associates with tumor grade, miR-194 expression independently associates with metastasis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e183 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Garcia-Roig Miami, FL More articles by this author Kateryna Kiselora Miami, FL More articles by this author Travis Yates Miami, FL More articles by this author Soum Lokeshwar Miami, FL More articles by this author Ezekiel Young Miami, FL More articles by this author Vincent Bird Gainesville, FL More articles by this author Murugesan Manoharan Miami, FL More articles by this author Vinita Lokeshwar Miami, FL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W1996304340 title "446 RENAL CELL CARCINOMA MICRO-RNA A MOLECULAR DETERMINANT OF METASTASIS" @default.
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