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Bringing hope to improve treatment in pancreatic ductal adenocarcinoma - a new tool for molecular profiling of KRAS mutations in tumor and plasma samples

2024-10-21Artigo de investigação Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
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.authorBaptista, Pedro Viana
dc.contributor.authorFernandes, Alexandra R.
dc.contributor.authorCravo, Marília
dc.date.accessioned2025-09-17T06:44:06Z
dc.date.available2025-09-17T06:44:06Z
dc.date.issued2024-10-21
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.eng
dc.identifier.citationBravo, A. C., Morão, B., Luz, A., & Dourado, R. et al. (2024). Bringing hope to improve treatment in pancreatic ductal adenocarcinoma - a new tool for molecular profiling of KRAS mutations in tumor and plasma samples. Cancers, 16(20), Article 3544. https://doi.org/10.3390/cancers16203544
dc.identifier.doi10.3390/cancers16203544
dc.identifier.eid85207677616
dc.identifier.issn2072-6694
dc.identifier.otheredae6fe1-96a7-4f7a-b59e-a24cbb8a566d
dc.identifier.pmcPMC11506488
dc.identifier.pmid39456638
dc.identifier.urihttp://hdl.handle.net/10400.14/54990
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAmplification refractory mutation system
dc.subjectARMS–HRMA
dc.subjectctDNA
dc.subjectKRAS mutations
dc.subjectLiquid biopsy
dc.subjectPancreatic cancer
dc.subjectPrognosis
dc.titleBringing hope to improve treatment in pancreatic ductal adenocarcinoma - a new tool for molecular profiling of KRAS mutations in tumor and plasma sampleseng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue20
oaire.citation.titleCancers
oaire.citation.volume16
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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