title: Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker.
abstract: BACKGROUND
  Since recent studies revealed the feasibility to detect blood-based microRNAs (miRNAs, miRs) in breast cancer (BC) patients a new field has been opened for circulating miRNAs as potential biomarkers in BC. In this pilot study, we evaluated to our knowledge for the first time whether distinct pattern of urinary miRNAs might be also applicable as innovative biomarkers for BC detection.
  
  
  METHODS
  Urinary miRNA expression levels of nine BC-related miRNAs (miR-21, miR-34a, miR-125b, miR-155, miR-195, miR-200b, miR-200c, miR-375, miR-451) from 24 untreated, primary BC patients and 24 healthy controls were quantified by realtime-PCR. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.
  
  
  RESULTS
  Significant differences were found in the expression of four BC-associated miRNAs quantified as median miRNA expression levels. Urinary miR-155 levels were significantly higher in BC patients compared to healthy controls (1.49vs.0.25; p < 0.001). In contrast, compared to healthy controls, BC patients exhibited significantly lower urinary expression levels of miR-21 (2.27vs.5.07; p < 0.001), miR-125b (0.71vs.1.62; p < 0.001), and miR-451 (0.02vs.0.59 p = 0.004), respectively. The ROC including all miRNAs as well as the group of the four significant deregulated miRNAs separated BC patients from healthy controls with a very high (area under the receiver operating characteristic curve [AUC] = 0.932) and high accuracy (AUC = 0.887), respectively.
  
  
  CONCLUSIONS
  We were able to demonstrate for the first time the feasibility to detect distinct BC-dependent urinary miRNA profiles. The expression levels of four urinary miRNAs were specifically altered in our cohort of BC patients compared to healthy controls. This distinct pattern offers the possibility for a specific discrimination between healthy women and primary BC patients. This sustains the potential role of urinary miRNAs as non-invasive innovative urine-based biomarkers for BC detection.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. thalia.erbes@uniklinik-freiburg.de.
authors.forename: Thalia
authors.initials: T
authors.lastname: Erbes
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. marc.hirschfeld@uniklinik-freiburg.de.|German Cancer Consortium (DKTK), Heidelberg, Germany. marc.hirschfeld@uniklinik-freiburg.de.|German Cancer Research Center (DKFZ), Heidelberg, Germany. marc.hirschfeld@uniklinik-freiburg.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Hirschfeld
authors.affiliation: Institute for Medical Biometry and Statistics, University Medical Center Freiburg, Freiburg, Germany. ruecker@imbi.uni-freiburg.de.
authors.forename: Gerta
authors.initials: G
authors.lastname: Rücker
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. markus.jaeger@uniklinik-freiburg.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Jaeger
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. jasmin.boas@uniklinik-freiburg.de.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Boas
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. severine.iborra@uniklinik-freiburg.de.
authors.forename: Severine
authors.initials: S
authors.lastname: Iborra
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. sebastian.mayer@uniklinik-freiburg.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. gerald.gitsch@uniklinik-freiburg.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gitsch
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany. elmar.stickeler@uniklinik-freiburg.de.|German Cancer Consortium (DKTK), Heidelberg, Germany. elmar.stickeler@uniklinik-freiburg.de.
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000652:urine*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000652:urine*; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs