Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs
Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of <i>EGFR</i>-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...
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MDPI AG
2021-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/6/1520 |
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| author | Alessandro Leonetti Mjriam Capula Roberta Minari Giulia Mazzaschi Alessandro Gregori Btissame El Hassouni Filippo Papini Paola Bordi Michela Verzè Amir Avan Marcello Tiseo Elisa Giovannetti |
| author_facet | Alessandro Leonetti Mjriam Capula Roberta Minari Giulia Mazzaschi Alessandro Gregori Btissame El Hassouni Filippo Papini Paola Bordi Michela Verzè Amir Avan Marcello Tiseo Elisa Giovannetti |
| author_sort | Alessandro Leonetti |
| collection | DOAJ |
| description | Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of <i>EGFR</i>-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 <i>EGFR</i>-mutated NSCLC patients. Methods: Plasma samples of 39 advanced <i>EGFR</i>-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) (<i>p</i> = 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 (<i>p</i> = 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 (<i>p</i> = 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 <i>EGFR</i>-mutated NSCLC. |
| first_indexed | 2024-03-10T10:20:31Z |
| format | Article |
| id | doaj.art-7a23652a75214cf3b35b2928e633ea77 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T10:20:31Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7a23652a75214cf3b35b2928e633ea772023-11-22T00:25:43ZengMDPI AGCells2073-44092021-06-01106152010.3390/cells10061520Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIsAlessandro Leonetti0Mjriam Capula1Roberta Minari2Giulia Mazzaschi3Alessandro Gregori4Btissame El Hassouni5Filippo Papini6Paola Bordi7Michela Verzè8Amir Avan9Marcello Tiseo10Elisa Giovannetti11Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsMedical Oncology Unit, University Hospital of Parma, 43126 Parma, ItalyMedical Oncology Unit, University Hospital of Parma, 43126 Parma, ItalyDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsMedical Oncology Unit, University Hospital of Parma, 43126 Parma, ItalyMedical Oncology Unit, University Hospital of Parma, 43126 Parma, ItalyDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The NetherlandsBackground: Resistance to EGFR-TKIs constitutes a major challenge for the management of <i>EGFR</i>-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 <i>EGFR</i>-mutated NSCLC patients. Methods: Plasma samples of 39 advanced <i>EGFR</i>-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) (<i>p</i> = 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 (<i>p</i> = 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 (<i>p</i> = 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 <i>EGFR</i>-mutated NSCLC.https://www.mdpi.com/2073-4409/10/6/1520miRNA<i>EGFR</i>-mutated NSCLCresponse to EGFR-TKItargeted therapy |
| spellingShingle | Alessandro Leonetti Mjriam Capula Roberta Minari Giulia Mazzaschi Alessandro Gregori Btissame El Hassouni Filippo Papini Paola Bordi Michela Verzè Amir Avan Marcello Tiseo Elisa Giovannetti Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs Cells miRNA <i>EGFR</i>-mutated NSCLC response to EGFR-TKI targeted therapy |
| title | Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs |
| title_full | Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs |
| title_fullStr | Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs |
| title_full_unstemmed | Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs |
| title_short | Dynamic Evaluation of Circulating miRNA Profile in <i>EGFR</i>-Mutated NSCLC Patients Treated with EGFR-TKIs |
| title_sort | dynamic evaluation of circulating mirna profile in i egfr i mutated nsclc patients treated with egfr tkis |
| topic | miRNA <i>EGFR</i>-mutated NSCLC response to EGFR-TKI targeted therapy |
| url | https://www.mdpi.com/2073-4409/10/6/1520 |
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