title: Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients.
abstract: Within the multicenter SUCCESS trial, we investigated the association of plasma microRNAs with different subtypes of invasive breast cancer.Six miRs (miR-16, miR-27a, miR-107, miR-130a, miR-132 and miR-146a) were selected from microarray profiling and further validated in plasma of 111 breast cancer patients before and after chemotherapy and 46 healthy women by quantitative real-time PCR.Plasma levels of miR-16 (p = 0.0001), miR-27a (p = 0.039) and miR-132 (p = 0.020) were higher in breast cancer patients before chemotherapy than healthy women. With the exception of miR-16, the increased levels of miR-27a (p = 0.035) and miR-132 (p = 0.025) decreased after chemotherapy to those observed in healthy women. Levels of miR-16 (p = 0.019), miR-107 (p = 0.036), miR-130a (p = 0.027) and miR-146a (p = 0.047) were different between lymph node -positive and -negative patients, while the levels of miR-130a (p = 0.001) and miR-146a (p = 0.025) also differed between HER2-positive and -negative status. Estrogen-receptor negative tumors displayed higher concentrations of circulating miR-107 than their counterparts (p = 0.035). However, overexpression of miR-107 in MCF-7 cells did not downregulate estrogen receptor protein. Altered expression levels of miR-107 influenced the migration and invasion behavior of MCF-7 and MDA-MB-231 cells.Our data indicate differential concentrations of plasma miR-16, miR-107, miR-130a and miR-146a in different breast cancer subtypes, suggesting a potential role of these miRs in breast cancer biology and tumor progression.
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Stückrath
authors.affiliation: First Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Ulm, Germany.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Jäger
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C549045:MIRN107 microRNA, human; C554019:MIRN130 microRNA, human; C542542:MIRN146 microRNA, human; C505362:MIRN16 microRNA, human; C508053:ERBB2 protein, human
keywords: cell-free miRs; chemotherapy; invasion; proliferation; tumor progression