Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial

BMC Medicine

Frederic Marmé¹  Carsten Denkert²  Peter A. Fasching³  Volkmar Müller⁴  Klaus Pantel⁵  Ines Stevic⁵  Heidi Schwarzenbach⁵  Karsten Weber⁶  Sibylle Loibl⁶  Michael Untch⁷  Christoph Salat⁸  Christian Schem⁹  Thomas Karn^1,10  Elmar Stickeler^1,11  Andreas Schneeweiss^1,12  Marion van Mackelenbergh^1,13 

[1] Center for Gynecological Oncology at University Women’s Hospital;Charite Berlin, Institute of Pathology and German Cancer Consortium (DKTK), Partner Site;Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg;Department of Gynecology, University Medical Center Hamburg-Eppendorf;Department of Tumor Biology, University Medical Center Hamburg-Eppendorf;GBG Forschungs GmbH;Helios Kliniken Berlin-Buch;Hämatoonkologische Schwerpunktpraxis;Mammazentrum Hamburg;University Women’s Hospital;Universitätsklinikum Aachen;Universitätsklinikum Heidelberg;Universitätsklinikums Schleswig-Holstein Kiel;

关键词: MicroRNAs;    Exosomes;    Breast cancer;    Triple negative;    HER2-positive;    Pathological complete response;   

DOI  :  10.1186/s12916-018-1163-y

来源: DOAJ

【 摘 要 】

Abstract Background The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). Methods First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization. Results Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR). Conclusion Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.

【 授权许可】

Unknown