Abstract
BackgroundThe 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).MethodsFirst, 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.ResultsQuantification 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).ConclusionOur 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.
Highlights
The focus of this study is to identify particular microRNA 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)
Triple-negative (TNBC) and HER2-positive tumors are associated with a worse prognosis, a more aggressive clinical outcome, and a higher risk for relapse than luminal-like tumors that are positive for hormone receptors [1]
Kodahl et al [27] showed that its expression levels were lower in serum of estrogen receptor (ER)-positive BC patients than healthy controls, whereas we show that its levels in HER2-positive patients who do not express ER were increased
Summary
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). MiRNAs derived from cancer-associated exosomes have been implicated in supporting or restraining tumor growth, conferring drug resistance, promoting recurrence, and preparing a metastatic niche [10]. Considering their biologic relevance, strategies to interfere with loading or delivery of exosomal oncogenic miRNAs might be used as a therapeutic approach
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