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Δευτέρα 19 Οκτωβρίου 2020

Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer.

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Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer.

Cancer Chemother Pharmacol. 2020 Oct 17;:

Authors: Zhang Z, Zhang L, Yu G, Sun Z, Wang T, Tian X, Duan X, Zhang C

Abstract
PURPOSE: This study aimed to investigate the predictive and prognostic roles of circulating exosomal miRNAs in breast cancer treated with trastuzumab-based chemotherapy.
METHODS: Circulating exosomal miRNAs from trastuzumab-resistant (n = 4) and -sensitive (n = 4) patients were profiled using miRNA microarray. The predictive and prognostic roles of filtered miRNAs were validated in 107 early-stage and 68 metastatic patients treated with trastuzumab-based chemotherapy through receiver-operating characteristic (ROC) curve analysis, logistic regression and Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis.
RESULTS: MiRNA microarray analysis revealed miR-1246 and miR-155 were the most up-regulated miRs in trastuzumab-resistant HER2-positive breast cancer patients, which were further validated in trastuzumab-resistant patient samples (n = 32) compared with trastuzumab sensitive ones (n = 36). MiR-1246 showed a ROC curve area of 0.750 with 78.1% sensitivity and 75% specificity in discriminating resistant from sensitive patients (p < 0.001), while miR-155 showed a ROC curve area of 0.877 with 68.8% sensitivity and 97.2% specificity (p < 0.001). Predictive factors and multivariate analysis showed that high levels of miR-1246 and miR-155 strongly predicted poor event-free survival (EFS) for early-stage patients, and poor progression-free survival (PFS) for metastatic patients. However, both miRNAs were revealed not to be associated with overall survival (OS). In addition, Kaplan-Meier survival analysis demonstrated that early-stage and metastatic patients with h igh expression of miR-1246 and miR-155 had poorer EFS or PFS, respectively, than those with decreased expression of both miRs.
CONCLUSIONS: This study demonstrated the valuable roles of circulating exosomal miR-1246 and miR-155 in distinguishing trastuzumab resistant from sensitive patients.

PMID: 33068176 [PubMed - as supplied by publisher]

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