title: MicroRNA promoter methylation: a new tool for accurate detection of urothelial carcinoma.
abstract: BACKGROUND
  Urothelial carcinoma (UC) is the most common cancer affecting the urinary system, worldwide. Lack of accurate early detection tools entails delayed diagnosis, precluding more efficient and timely treatment. In a previous study, we found that miR-129-2 and miR-663a were differentially methylated in UC compared with other genitourinary tract malignancies. Here, we evaluated the diagnostic performance of those microRNAs in urine.
  
  
  METHODS
  Promoter methylation levels of miR-129-2 and miR-663a were assessed, using real-time quantitative methylation-specific PCR, in UC tissue samples (using normal urothelium as control) and, subsequently, in urine samples from UC and other genitourinary malignancies. Diagnostic and prognostic performances were evaluated by receiver operator characteristics curve and survival analyses, respectively.
  
  
  RESULTS
  Promoter methylation levels of both microRNAs were significantly higher in UC tissue samples compared with normal urothelium. In urine, the assay was able to distinguish UC from other genitourinary tract carcinomas with 87.7% sensitivity and 84% specificity, resulting in 85.85% overall accuracy.
  
  
  CONCLUSIONS
  This panel of miRNAs promoter methylation accurately detects UC in urine, comparing well with other promising epigenetic-based biomarkers. This may constitute the basis for a non-invasive assay to detect UC.
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Nuno André
authors.initials: NA
authors.lastname: Padrão
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Monteiro-Reis
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Torres-Ferreira
authors.affiliation: Department of Epidemiology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Antunes
authors.affiliation: Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Leça
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Montezuma
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Ramalho-Carvalho
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Dias
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Monteiro
authors.affiliation: Department of Urology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS) - University of Porto, Rua de Jorge Viterbo Ferreira n.º 228, Porto 4050-313, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.|Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS) - University of Porto, Rua de Jorge Viterbo Ferreira n.º 228, Porto 4050-313, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019459:Urothelium / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human