Publicação
Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma
| Resumo: | Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis. |
|---|---|
| Autores principais: | Bravo, Ana Catarina |
| Outros Autores: | Morão, Bárbara; Luz, André; Dourado, Rúben; Oliveira, Beatriz; Guedes, Ana; Moreira-Barbosa, Catarina; Fidalgo, Catarina; Mascarenhas-Lemos, Luís; Costa-Santos, Maria Pia; Maio, Rui; Paulino, Jorge; Viana Baptista, Pedro; Fernandes, Alexandra R.; Cravo, Marília |
| Assunto: | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| Ano: | 2024 |
| 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_ | 1868983746110160896 |
|---|---|
| author | Bravo, Ana Catarina |
| author2 | Morão, Bárbara Luz, André Dourado, Rúben Oliveira, Beatriz Guedes, Ana Moreira-Barbosa, Catarina Fidalgo, Catarina Mascarenhas-Lemos, Luís Costa-Santos, Maria Pia Maio, Rui Paulino, Jorge Viana Baptista, Pedro Fernandes, Alexandra R. Cravo, Marília |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Bravo, Ana Catarina Morão, Bárbara Luz, André Dourado, Rúben Oliveira, Beatriz Guedes, Ana Moreira-Barbosa, Catarina Fidalgo, Catarina Mascarenhas-Lemos, Luís Costa-Santos, Maria Pia Maio, Rui Paulino, Jorge Viana Baptista, Pedro Fernandes, Alexandra R. Cravo, Marília |
| author_role | author |
| contributor_name_str_mv | DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit Faculdade de Ciências e Tecnologia (FCT) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Bravo, Ana Catarina\"},{\"Person.name\":\"Morão, Bárbara\"},{\"Person.name\":\"Luz, André\"},{\"Person.name\":\"Dourado, Rúben\"},{\"Person.name\":\"Oliveira, Beatriz\"},{\"Person.name\":\"Guedes, Ana\"},{\"Person.name\":\"Moreira-Barbosa, Catarina\"},{\"Person.name\":\"Fidalgo, Catarina\"},{\"Person.name\":\"Mascarenhas-Lemos, Luís\"},{\"Person.name\":\"Costa-Santos, Maria Pia\"},{\"Person.name\":\"Maio, Rui\"},{\"Person.name\":\"Paulino, Jorge\"},{\"Person.name\":\"Viana Baptista, Pedro\"},{\"Person.name\":\"Fernandes, Alexandra R.\"},{\"Person.name\":\"Cravo, Marília\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit Faculdade de Ciências e Tecnologia (FCT) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Bravo, Ana Catarina Morão, Bárbara Luz, André Dourado, Rúben Oliveira, Beatriz Guedes, Ana Moreira-Barbosa, Catarina Fidalgo, Catarina Mascarenhas-Lemos, Luís Costa-Santos, Maria Pia Maio, Rui Paulino, Jorge Viana Baptista, Pedro Fernandes, Alexandra R. Cravo, Marília |
| datacite.date.Accepted.fl_str_mv | 2024-10-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2025-02-24T21:50:54Z |
| datacite.date.embargoed.fl_str_mv | 2025-02-24T21:50:54Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| datacite.titles.title.fl_str_mv | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples |
| dc.contributor.none.fl_str_mv | DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit Faculdade de Ciências e Tecnologia (FCT) MDPI - Multidisciplinary Digital Publishing Institute RUN |
| dc.creator.none.fl_str_mv | Bravo, Ana Catarina Morão, Bárbara Luz, André Dourado, Rúben Oliveira, Beatriz Guedes, Ana Moreira-Barbosa, Catarina Fidalgo, Catarina Mascarenhas-Lemos, Luís Costa-Santos, Maria Pia Maio, Rui Paulino, Jorge Viana Baptista, Pedro Fernandes, Alexandra R. Cravo, Marília |
| dc.date.Accepted.fl_str_mv | 2024-10-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2025-02-24T21:50:54Z |
| dc.date.embargoed.fl_str_mv | 2025-02-24T21:50:54Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/179688 |
| 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 | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| dc.title.fl_str_mv | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/bebf41a5-fe31-4b06-ae15-7fdf07b54b26/download |
| funder_facet_str_mv | FCT{{{_:::_}}}Fundação para a Ciência e a Tecnologia FCT{{{_:::_}}}Fundação para a Ciência e a Tecnologia |
| funding.funder.alternateName_str_mv | FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | 6817 - DCRRNI ID OE |
| id | run_d0edc8d19d115d9ac42dd82a8cf330c0 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/179688 |
| 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:10362/179688 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Bravo, Ana Catarina Morão, Bárbara Luz, André Dourado, Rúben Oliveira, Beatriz Guedes, Ana Moreira-Barbosa, Catarina Fidalgo, Catarina Mascarenhas-Lemos, Luís Costa-Santos, Maria Pia Maio, Rui Paulino, Jorge Viana Baptista, Pedro Fernandes, Alexandra R. Cravo, Marília |
| publishDate | 2024 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenBackground/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.application/pdfenBringing Hope to Improve Treatment in Pancreatic Ductal AdenocarcinomaSubtitleenA New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma SamplesBravo, Ana CatarinaMorão, BárbaraLuz, AndréDourado, RúbenOliveira, BeatrizGuedes, AnaMoreira-Barbosa, CatarinaFidalgo, CatarinaMascarenhas-Lemos, LuísCosta-Santos, Maria PiaMaio, RuiPaulino, JorgeViana Baptista, PedroFernandes, Alexandra R.Cravo, MaríliaDCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitFaculdade de Ciências e Tecnologia (FCT)MDPI - Multidisciplinary Digital Publishing InstituteHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2072-6694URNIsPartOfPURE: 103141167URNIsPartOfPURE UUID: 6c983e7a-fadd-4cce-99a6-514ebd03cc9fURNIsPartOfWOS: 001341494800001URNIsPartOfPubMed: 39456638URNIsPartOfScopus: 85207677616URNIsPartOfORCID: /0000-0001-5255-7095/work/178851782URNIsPartOfORCID: /0000-0003-2054-4438/work/178851952DOIIsPartOf10.3390/cancers162035442025-02-24T21:50:54Z2024-102024-10-01T00:00:00ZHandlehttp://hdl.handle.net/10362/179688http://purl.org/coar/access_right/c_abf2open accessamplification refractory mutation systemARMS–HRMActDNAKRAS mutationsliquid biopsypancreatic cancerprognosisOncologyCancer ResearchSDG 3 - Good Health and Well-being2380966 bytesFundação para a Ciência e a TecnologiaApplied Molecular Biosciences Unit6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaGold4Exomarkers: Modulation of exosome biomarkers of drug resistance via gold nanoconjugatesOECrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/bebf41a5-fe31-4b06-ae15-7fdf07b54b26/download |
| spellingShingle | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma Bravo, Ana Catarina amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| status | SINGLETON |
| subject.fl_str_mv | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| title | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| title_full | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| title_short | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| title_sort | Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma |
| topic | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| topic_facet | amplification refractory mutation system ARMS–HRMA ctDNA KRAS mutations liquid biopsy pancreatic cancer prognosis Oncology Cancer Research SDG 3 - Good Health and Well-being |
| url | http://hdl.handle.net/10362/179688 |
| visible | 1 |