title: Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression.
abstract: BACKGROUND
  MicroRNAs (miRs) are small, noncoding RNAs that target genes involved in tumor development and progression. In the current study, we investigated the use of circulating miR concentrations as biomarkers in the serum of breast cancer patients.
  
  
  METHODS
  We analyzed serum samples from 120 patients with primary breast cancer after surgery and before chemotherapy (M0, classified into 3 subgroups of 40 patients with progesterone/estrogen-positive, HER2-positive, and triple-negative cancer), 32 patients with overt metastasis (M1), and 40 healthy women. Using quantitative TaqMan MicroRNA PCR, we measured the relative concentrations of 6 circulating microRNAs (miR-10b, -17, -34a, -93, -155, and -373) known to be relevant for tumor development and progression. The data were correlated with clinicopathologic risk factors, with particular reference to HER2 and hormone receptor status of the primary tumor and the presence of metastases.
  
  
  RESULTS
  The relative serum concentrations of circulating miR-34a [P = 0.013, area under the curve (AUC) 0.636], miR-93 (P = 0.001, AUC 0.699), and miR-373 (P = 0.0001, AUC 0.879) were significantly different between M0 breast cancer patients and healthy women, whereas miR-17 (P = 0.002, AUC 0.679) and miR-155 (P = 0.0001, AUC 0.781) were differently expressed between M0 and M1 patients. Increased concentrations of miR-373 were associated with negative HER2 status of the primary tumor (P = 0.0001). Deregulated concentrations of miR-17 (P = 0.019) and miR-34a (P = 0.029) were detected in patients with progesterone/estrogen receptor-positive and -negative status, respectively.
  
  
  CONCLUSIONS
  Our findings indicate that serum concentrations of deregulated microRNAs may be linked to a particular biology of breast carcinomas favoring progression and metastatic spread.
authors.affiliation: Department of Tumor Biology.
authors.forename: Corinna
authors.initials: C
authors.lastname: Eichelser
authors.forename: Dieter
authors.initials: D
authors.lastname: Flesch-Janys
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000473:pathology
chemical_list: D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C524942:MIRN155 microRNA, human; C524941:MIRN17 microRNA, human; C522425:MIRN34 microRNA, human; C527114:MIRN373 microRNA, human; C508053:ERBB2 protein, human