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Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073028/ https://www.ncbi.nlm.nih.gov/pubmed/32085669 http://dx.doi.org/10.3390/ijms21041386 |
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author | Di Cosimo, Serena Appierto, Valentina Pizzamiglio, Sara Silvestri, Marco Baselga, José Piccart, Martine Huober, Jens Izquierdo, Miguel de la Pena, Lorena Hilbers, Florentine S. de Azambuja, Evandro Untch, Michael Pusztai, Lajos Pritchard, Kathleen Nuciforo, Paolo Vincent-Salomon, Anne Symmans, Fraser Apolone, Giovanni de Braud, Filippo G. Iorio, Marilena V. Verderio, Paolo Daidone, Maria Grazia |
author_facet | Di Cosimo, Serena Appierto, Valentina Pizzamiglio, Sara Silvestri, Marco Baselga, José Piccart, Martine Huober, Jens Izquierdo, Miguel de la Pena, Lorena Hilbers, Florentine S. de Azambuja, Evandro Untch, Michael Pusztai, Lajos Pritchard, Kathleen Nuciforo, Paolo Vincent-Salomon, Anne Symmans, Fraser Apolone, Giovanni de Braud, Filippo G. Iorio, Marilena V. Verderio, Paolo Daidone, Maria Grazia |
author_sort | Di Cosimo, Serena |
collection | PubMed |
description | Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%–68%), and 44% (95%CI 22%–69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23–9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%–81%) and 0% (95%CI 0%–31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy. |
format | Online Article Text |
id | pubmed-7073028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70730282020-03-19 Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy Di Cosimo, Serena Appierto, Valentina Pizzamiglio, Sara Silvestri, Marco Baselga, José Piccart, Martine Huober, Jens Izquierdo, Miguel de la Pena, Lorena Hilbers, Florentine S. de Azambuja, Evandro Untch, Michael Pusztai, Lajos Pritchard, Kathleen Nuciforo, Paolo Vincent-Salomon, Anne Symmans, Fraser Apolone, Giovanni de Braud, Filippo G. Iorio, Marilena V. Verderio, Paolo Daidone, Maria Grazia Int J Mol Sci Article Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%–68%), and 44% (95%CI 22%–69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23–9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%–81%) and 0% (95%CI 0%–31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy. MDPI 2020-02-18 /pmc/articles/PMC7073028/ /pubmed/32085669 http://dx.doi.org/10.3390/ijms21041386 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Di Cosimo, Serena Appierto, Valentina Pizzamiglio, Sara Silvestri, Marco Baselga, José Piccart, Martine Huober, Jens Izquierdo, Miguel de la Pena, Lorena Hilbers, Florentine S. de Azambuja, Evandro Untch, Michael Pusztai, Lajos Pritchard, Kathleen Nuciforo, Paolo Vincent-Salomon, Anne Symmans, Fraser Apolone, Giovanni de Braud, Filippo G. Iorio, Marilena V. Verderio, Paolo Daidone, Maria Grazia Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title | Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title_full | Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title_fullStr | Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title_full_unstemmed | Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title_short | Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy |
title_sort | early modulation of circulating micrornas levels in her2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073028/ https://www.ncbi.nlm.nih.gov/pubmed/32085669 http://dx.doi.org/10.3390/ijms21041386 |
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