Aberrant plasma levels of circulatingmiR-16, miR-107, miR-130aandmiR-146aare associated with lymph node metastasis and receptor status of breast cancer patients

// Isabel Stückrath 1 , Brigitte Rack 2 , Wolfgang Janni 3 , Bernadette Jäger 3 , Klaus Pantel 1 and Heidi Schwarzenbach 1 1 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany 2 First Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Germany 3 Department of Gynecology and Obstetrics, University Hospital Ulm, Germany Correspondence to: Heidi Schwarzenbach, email: // Keywords : cell-free miRs, chemotherapy, invasion, proliferation, tumor progression Received : December 22, 2014 Accepted : April 03, 2015 Published : April 19, 2015 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.