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Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmat...

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Autores principales: Leonetti, Alessandro, Capula, Mjriam, Minari, Roberta, Mazzaschi, Giulia, Gregori, Alessandro, El Hassouni, Btissame, Papini, Filippo, Bordi, Paola, Verzè, Michela, Avan, Amir, Tiseo, Marcello, Giovannetti, Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235748/
https://www.ncbi.nlm.nih.gov/pubmed/34208765
http://dx.doi.org/10.3390/cells10061520
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author Leonetti, Alessandro
Capula, Mjriam
Minari, Roberta
Mazzaschi, Giulia
Gregori, Alessandro
El Hassouni, Btissame
Papini, Filippo
Bordi, Paola
Verzè, Michela
Avan, Amir
Tiseo, Marcello
Giovannetti, Elisa
author_facet Leonetti, Alessandro
Capula, Mjriam
Minari, Roberta
Mazzaschi, Giulia
Gregori, Alessandro
El Hassouni, Btissame
Papini, Filippo
Bordi, Paola
Verzè, Michela
Avan, Amir
Tiseo, Marcello
Giovannetti, Elisa
author_sort Leonetti, Alessandro
collection PubMed
description Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in EGFR-mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR-mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR. Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in EGFR-mutated NSCLC.
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spelling pubmed-82357482021-06-27 Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs Leonetti, Alessandro Capula, Mjriam Minari, Roberta Mazzaschi, Giulia Gregori, Alessandro El Hassouni, Btissame Papini, Filippo Bordi, Paola Verzè, Michela Avan, Amir Tiseo, Marcello Giovannetti, Elisa Cells Article Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in EGFR-mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR-mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR. Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in EGFR-mutated NSCLC. MDPI 2021-06-16 /pmc/articles/PMC8235748/ /pubmed/34208765 http://dx.doi.org/10.3390/cells10061520 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leonetti, Alessandro
Capula, Mjriam
Minari, Roberta
Mazzaschi, Giulia
Gregori, Alessandro
El Hassouni, Btissame
Papini, Filippo
Bordi, Paola
Verzè, Michela
Avan, Amir
Tiseo, Marcello
Giovannetti, Elisa
Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title_full Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title_fullStr Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title_full_unstemmed Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title_short Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs
title_sort dynamic evaluation of circulating mirna profile in egfr-mutated nsclc patients treated with egfr-tkis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235748/
https://www.ncbi.nlm.nih.gov/pubmed/34208765
http://dx.doi.org/10.3390/cells10061520
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