Publicação
MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma
| Resumo: | Background: Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients. Methods: This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs. Results: NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival. Discussion: Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance. |
|---|---|
| Autores principais: | Bergantim, Rui |
| Outros Autores: | Peixoto da Silva, Sara; Pinto, Vanessa; Pereira, Joana M.; Sousa, Diana; Trigo, Fernanda; Matthiesen, Rune; Matthiesen, Rune; Guimarães, José E.; Vasconcelos, M. Helena |
| Assunto: | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983877828083712 |
|---|---|
| author | Bergantim, Rui |
| author2 | Peixoto da Silva, Sara Pinto, Vanessa Pereira, Joana M. Sousa, Diana Trigo, Fernanda Matthiesen, Rune Matthiesen, Rune Guimarães, José E. Vasconcelos, M. Helena |
| author2_role | author author author author author author author author author |
| author_facet | Bergantim, Rui Peixoto da Silva, Sara Pinto, Vanessa Pereira, Joana M. Sousa, Diana Trigo, Fernanda Matthiesen, Rune Matthiesen, Rune Guimarães, José E. Vasconcelos, M. Helena |
| author_role | author |
| contributor_name_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Frontiers Media RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Bergantim, Rui\"},{\"Person.name\":\"Peixoto da Silva, Sara\"},{\"Person.name\":\"Pinto, Vanessa\"},{\"Person.name\":\"Pereira, Joana M.\"},{\"Person.name\":\"Sousa, Diana\"},{\"Person.name\":\"Trigo, Fernanda\"},{\"Person.name\":\"Matthiesen, Rune\"},{\"Person.name\":\"Matthiesen, Rune\",\"Person.identifier.orcid\":\"0000-0002-6353-2616\"},{\"Person.name\":\"Guimarães, José E.\"},{\"Person.name\":\"Vasconcelos, M. Helena\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Frontiers Media RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Bergantim, Rui Peixoto da Silva, Sara Pinto, Vanessa Pereira, Joana M. Sousa, Diana Trigo, Fernanda Matthiesen, Rune Matthiesen, Rune Guimarães, José E. Vasconcelos, M. Helena |
| datacite.date.Accepted.fl_str_mv | 2025-04-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2025-05-07T21:35:08Z |
| datacite.date.embargoed.fl_str_mv | 2025-05-07T21:35:08Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| datacite.titles.title.fl_str_mv | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma a preliminary study |
| dc.contributor.none.fl_str_mv | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Frontiers Media RUN |
| dc.creator.none.fl_str_mv | Bergantim, Rui Peixoto da Silva, Sara Pinto, Vanessa Pereira, Joana M. Sousa, Diana Trigo, Fernanda Matthiesen, Rune Matthiesen, Rune Guimarães, José E. Vasconcelos, M. Helena |
| dc.date.Accepted.fl_str_mv | 2025-04-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2025-05-07T21:35:08Z |
| dc.date.embargoed.fl_str_mv | 2025-05-07T21:35:08Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/182826 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| dc.title.fl_str_mv | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma a preliminary study |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Background: Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients. Methods: This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs. Results: NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival. Discussion: Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/f7f65fa5-0a93-4f3a-9b32-16ccb87b2be0/download |
| id | run_d75f0538fa94dac3cdaccb94d2cb2721 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/182826 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/182826 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Bergantim, Rui Peixoto da Silva, Sara Pinto, Vanessa Pereira, Joana M. Sousa, Diana Trigo, Fernanda Matthiesen, Rune Matthiesen, Rune Matthiesen, Rune https://www.ciencia-id.pt/BB1A-A606-EE77 BB1A-A606-EE77 http://orcid.org/0000-0002-6353-2616 0000-0002-6353-2616 Guimarães, José E. Vasconcelos, M. Helena |
| publishDate | 2025 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
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| spelling | engenBackground: Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients. Methods: This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs. Results: NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival. Discussion: Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.application/pdfenMicroRNA-665 and its potential role in drug response and survival outcomes in multiple myelomaSubtitleena preliminary studyBergantim, RuiPeixoto da Silva, SaraPinto, VanessaPereira, Joana M.Sousa, DianaTrigo, FernandaMatthiesen, RunePersonalMatthiesen, RuneDSpacehttp://dspace.org/items/67181d3c-b83e-4151-9a74-0ea14aeb7f05DSpacehttp://dspace.org/items/67181d3c-b83e-4151-9a74-0ea14aeb7f05MatthiesenRuneCiência IDhttps://www.ciencia-id.ptBB1A-A606-EE77ORCIDhttp://orcid.org0000-0002-6353-2616Scopus Author IDhttps://www.scopus.com9741897800Guimarães, José E.Vasconcelos, M. HelenaNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSFrontiers MediaHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf1663-9812URNIsPartOfPURE: 115627998URNIsPartOfPURE UUID: 938efa16-728a-47f0-842a-16ca64bf4ac1URNIsPartOfScopus: 105003054037DOIIsPartOf10.3389/fphar.2025.14658142025-05-07T21:35:08Z2025-042025-04-01T00:00:00ZHandlehttp://hdl.handle.net/10362/182826http://purl.org/coar/access_right/c_abf2open accessbiomarkersdrug resistancedrug responsemiRNAsmultiple myelomaPharmacologyPharmacology (medical)2213642 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/f7f65fa5-0a93-4f3a-9b32-16ccb87b2be0/download |
| spellingShingle | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma Bergantim, Rui biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| status | SINGLETON |
| subject.fl_str_mv | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| title | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| title_full | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| title_fullStr | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| title_full_unstemmed | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| title_short | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| title_sort | MicroRNA-665 and its potential role in drug response and survival outcomes in multiple myeloma |
| topic | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| topic_facet | biomarkers drug resistance drug response miRNAs multiple myeloma Pharmacology Pharmacology (medical) |
| url | http://hdl.handle.net/10362/182826 |
| visible | 1 |