title: Oncogenic microRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum.
abstract: BACKGROUND
  MicroRNAs (miRs) represent a distinct class of posttranscriptional modulators of gene expression with remarkable stability in sera. Several miRs are oncogenic (oncomiRs) and are deregulated in the pathogenesis of breast cancer and function to inhibit tumor suppressors. Routine blood monitoring of these circulating tumor-derived products could be of significant benefit to the diagnosis and relapse detection of early-stage breast cancer (EBC) patients.
  
  
  METHODS
  Aim of this project was to determine expression of miR-155, miR-19a, miR-181b, miR-24, relative to let-7a in sera of 63 patients with EBC and 21 healthy controls. Longitudinal multivariate data analysis was performed to stochastically model the serum levels of each of the oncomiRs during disease phases: from diagnosis, after surgery, and following chemo/radiotherapy. Moreover, this analysis was utilized to evaluate oncomiR levels in EBC patients subgrouped using current clinical prognostic factors including HER2, Ki-67, and grade III.
  
  
  RESULTS
  EBC patients significantly over-express the oncomiRs at the time of diagnosis. Following surgical resection the serum levels of miR-155, miR-181b, and miR-24 significantly decreased (p = 1.89e-05, 5.41e-06, and 0.00638, respectively) whereas the miR-19a decreased significantly after the therapy (p = 0.00869). Furthermore, in case of high-risk patients serum levels of miR-155, miR-19a, miR-181b, and miR-24 are significantly more abundant in comparison to low-risk group (p = 0.026, 0.02567, 0.0250, and 0.00990) and show a decreasing trend upon therapy.
  
  
  CONCLUSIONS
  OncomiRs are significantly more abundant in the sera of EBC patients compared to controls at diagnosis. Differences in oncomiR levels reflecting EBC risk were also observed. Testing the oncomiRs may be useful for diagnostic purpose and possibly also for relapse detection in follow-up studies of EBC.
authors.forename: Marek
authors.initials: M
authors.lastname: Sochor
authors.forename: Petra
authors.initials: P
authors.lastname: Basova
authors.forename: Michal
authors.initials: M
authors.lastname: Pesta
authors.forename: Nina
authors.initials: N
authors.lastname: Dusilkova
authors.forename: Jiri
authors.initials: J
authors.lastname: Bartos
authors.forename: Pavel
authors.initials: P
authors.lastname: Burda
authors.forename: Vit
authors.initials: V
authors.lastname: Pospisil
authors.affiliation: 1st Faculty of Medicine, Institute of Pathological Physiology, Charles University in Prague, Prague, Czech Republic. tstopka@lf1.cuni.cz.
authors.forename: Tomas
authors.initials: T
authors.lastname: Stopka
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C549214:MIRN19A microRNA, human; C543845:MIRN24 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs