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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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