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Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma

2024-10Artigo científico Acesso aberto
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dc.contributor.authorBravo, Ana Catarina
dc.contributor.authorMorão, Bárbara
dc.contributor.authorLuz, André
dc.contributor.authorDourado, Rúben
dc.contributor.authorOliveira, Beatriz
dc.contributor.authorGuedes, Ana
dc.contributor.authorMoreira-Barbosa, Catarina
dc.contributor.authorFidalgo, Catarina
dc.contributor.authorMascarenhas-Lemos, Luís
dc.contributor.authorCosta-Santos, Maria Pia
dc.contributor.authorMaio, Rui
dc.contributor.authorPaulino, Jorge
dc.contributor.authorViana Baptista, Pedro
dc.contributor.authorFernandes, Alexandra R.
dc.contributor.authorCravo, Marília
dc.contributor.institutionDCV - Departamento de Ciências da Vida
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2025-02-24T21:50:54Z
dc.date.available2025-02-24T21:50:54Z
dc.date.issued2024-10
dc.descriptionThis work (project reference LH.INV.F2019016) is partially co-financed by Luz da Hospital Lisboa under the initiative “Luz Investigação.” © 2024 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.abstractBackground/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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent18
dc.format.extent2380966
dc.identifier.doi10.3390/cancers16203544
dc.identifier.issn2072-6694
dc.identifier.otherPURE: 103141167
dc.identifier.otherPURE UUID: 6c983e7a-fadd-4cce-99a6-514ebd03cc9f
dc.identifier.otherWOS: 001341494800001
dc.identifier.otherPubMed: 39456638
dc.identifier.otherScopus: 85207677616
dc.identifier.otherORCID: /0000-0001-5255-7095/work/178851782
dc.identifier.otherORCID: /0000-0003-2054-4438/work/178851952
dc.identifier.urihttp://hdl.handle.net/10362/179688
dc.identifier.urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=nova_api&SrcAuth=WosAPI&KeyUT=WOS:001341494800001&DestLinkType=FullRecord&DestApp=WOS_CPL
dc.identifier.urlhttps://www.scopus.com/pages/publications/85207677616
dc.language.isoeng
dc.peerreviewedyes
dc.relationFunding Information: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
dc.relationApplied Molecular Biosciences Unit
dc.relationinfo:eu-repo/grantAgreement/FCT//2020.07660.BD/PT
dc.relationGold4Exomarkers: Modulation of exosome biomarkers of drug resistance via gold nanoconjugates
dc.subjectamplification refractory mutation system
dc.subjectARMS–HRMA
dc.subjectctDNA
dc.subjectKRAS mutations
dc.subjectliquid biopsy
dc.subjectpancreatic cancer
dc.subjectprognosis
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleBringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinomaen
dc.title.subtitleA New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samplesen
dc.typejournal article
degois.publication.issue20
degois.publication.titleCancers
degois.publication.volume16
dspace.entity.typePublication
oaire.awardNumberUIDB/04378/2020
oaire.awardNumberLA/P/0140/2020
oaire.awardNumber2020.07660.BD
oaire.awardNumber2022.12161.BD
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleGold4Exomarkers: Modulation of exosome biomarkers of drug resistance via gold nanoconjugates
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso para Atribuição do Estatuto e Financiamento de Laboratórios Associados (LA)/LA%2FP%2F0140%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//2020.07660.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/2022.12161.BD/PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamConcurso para Atribuição do Estatuto e Financiamento de Laboratórios Associados (LA)
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
relation.isProjectOfPublicatione07cf232-4705-4b5b-b2c4-af8f25311076
relation.isProjectOfPublicationecd6da06-821d-4fff-933b-319b334dc19a
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relation.isProjectOfPublication4355b960-bce9-4acf-98f5-ff120620a69c
relation.isProjectOfPublication.latestForDiscovery4355b960-bce9-4acf-98f5-ff120620a69c

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