title: Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection.
abstract: BACKGROUND
  The identification of novel biomarkers for early breast cancer detection would be a great advance. Because of their role in tumorigenesis and stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. Our aim was to identify miRNAs deregulated in breast tumors and evaluate the potential of circulating miRNAs in breast cancer detection.
  
  
  METHODS
  We conducted miRNA expression profiling of 1919 human miRNAs in paraffin-embedded tissue from 122 breast tumors and 11 healthy breast tissue samples. Differential expression analysis was performed, and a microarray classifier was generated. The most relevant miRNAs were analyzed in plasma from 26 healthy individuals and 83 patients with breast cancer (36 before and 47 after treatment) and validated in 116 healthy individuals and 114 patients before treatment.
  
  
  RESULTS
  We identified a large number of miRNAs deregulated in breast cancer and generated a 25-miRNA microarray classifier that discriminated breast tumors with high diagnostic sensitivity and specificity. Ten miRNAs were selected for further investigation, of which 4 (miR-505-5p, miR-125b-5p, miR-21-5p, and miR-96-5p) were significantly overexpressed in pretreated patients with breast cancer compared with healthy individuals in 2 different series of plasma. MiR-505-5p and miR-96-5p were the most valuable biomarkers (area under the curve 0.72). Moreover, the expression levels of miR-3656, miR-505-5p, and miR-21-5p were decreased in a group of treated patients.
  
  
  CONCLUSIONS
  Circulating miRNAs reflect the presence of breast tumors. The identification of deregulated miRNAs in plasma of patients with breast cancer supports the use of circulating miRNAs as a method for early breast cancer detection.
authors.affiliation: Human Cancer Genetics Programme and.
authors.forename: Nerea
authors.initials: N
authors.lastname: Matamala
authors.affiliation: Pathology Service and.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Vargas
authors.affiliation: Pathology Service and.
authors.forename: Ricardo
authors.initials: R
authors.lastname: González-Cámpora
authors.affiliation: Projects Unit, Sistemas Genómicos, Valencia, Spain;
authors.forename: Rebeca
authors.initials: R
authors.lastname: Miñambres
authors.affiliation: Surgery Service and.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Arias
authors.affiliation: Pathology Service, Hospital Monte Naranco, Oviedo, Spain;
authors.forename: Primitiva
authors.initials: P
authors.lastname: Menéndez
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain;
authors.forename: Eduardo
authors.initials: E
authors.lastname: Andrés-León
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain;
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.affiliation: Human Cancer Genetics Programme and.
authors.forename: Kira
authors.initials: K
authors.lastname: Yanowsky
authors.affiliation: Medical Oncology Service, Hospital Virgen de la Macarena, Sevilla, Spain;
authors.forename: Julio
authors.initials: J
authors.lastname: Calvete-Candenas
authors.affiliation: Human Cancer Genetics Programme and Spanish Network in Rare Diseases (CIBERER), Madrid, Spain;
authors.forename: Lucía
authors.initials: L
authors.lastname: Inglada-Pérez
authors.affiliation: Molecular Genetics Unit, Research Institute of Rare Diseases (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Delgado
authors.affiliation: Human Cancer Genetics Programme and Spanish Network in Rare Diseases (CIBERER), Madrid, Spain; jbenitez@cnio.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; C574053:MIRN505 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs