TY  - JOUR
A1  - Stevic, Ines
A1  - Müller, Volkmar
A1  - Weber, Karsten E.
A1  - Fasching, Peter Andreas
A1  - Karn, Thomas
A1  - Marmé, Frederic
A1  - Schem, Christian
A1  - Stickeler, Elmar
A1  - Denkert, Carsten Michael
A1  - Mackelenbergh, Marion Tina van
A1  - Salat, Christoph
A1  - Schneeweiss, Andreas
A1  - Pantel, Klaus
A1  - Loibl, Sibylle
A1  - Untch, Michael
A1  - Schwarzenbach, Heidi
T1  - Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial
T2  - BMC medicine
N2  - 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.
KW  - MicroRNAs
KW  - Exosomes
KW  - Breast cancer
KW  - Triple negative
KW  - HER2-positive
KW  - Pathological complete response
KW  - Neoadjuvant therapy
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47693
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-476931
SN  - 1741-7015
N1  - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 16
IS  - 1, Art. 179
SP  - 1
EP  - 16
PB  - BioMed Central ; Springer
CY  - London ; Berlin ; Heidelberg [u. a.]
ER  -