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

  • 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.

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Author:Ines Stevic, Volkmar MüllerORCiDGND, Karsten E. Weber, Peter Andreas FaschingORCiDGND, Thomas Karn, Frederic Marmé, Christian Schem, Elmar Stickeler, Carsten Michael Denkert, Marion Tina van Mackelenbergh, Christoph Salat, Andreas SchneeweissORCiDGND, Klaus PantelORCiDGND, Sibylle LoiblORCiDGND, Michael UntchORCiDGND, Heidi Schwarzenbach
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30301470
Parent Title (English):BMC medicine
Publisher:BioMed Central ; Springer
Place of publication:London ; Berlin ; Heidelberg [u. a.]
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/10/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/10/16
Tag:Breast cancer; Exosomes; HER2-positive; MicroRNAs; Neoadjuvant therapy; Pathological complete response; Triple negative
Issue:1, Art. 179
Page Number:16
First Page:1
Last Page:16
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.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0