{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:26Z","timestamp":1760146346945,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Luz da Hospital Lisboa"},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia"},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO"},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013HRMA 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\u20131, 57% with resectable disease. ARMS\u2013HRMA 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\u20133.028, p = 0.029; HR 2.081, 95% CI 1.014\u20134.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013\u20133.049, p = 0.045; HR 2.229, 95% CI 1.082\u20134.594, p = 0.030, respectively). Conclusions: ARMS\u2013HRMA 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.<\/jats:p>","DOI":"10.3390\/cancers16203544","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T08:53:11Z","timestamp":1729500791000},"page":"3544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma\u2014A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples"],"prefix":"10.3390","volume":"16","author":[{"given":"Ana Catarina","family":"Bravo","sequence":"first","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"}]},{"given":"B\u00e1rbara","family":"Mor\u00e3o","sequence":"additional","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-9033","authenticated-orcid":false,"given":"Andr\u00e9","family":"Luz","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2953-9985","authenticated-orcid":false,"given":"R\u00faben","family":"Dourado","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-4703","authenticated-orcid":false,"given":"Beatriz","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"given":"Ana","family":"Guedes","sequence":"additional","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"},{"name":"Hospital da Luz Learning Health, Luz Sa\u00fade, 1500-650 Lisboa, Portugal"}]},{"given":"Catarina","family":"Moreira-Barbosa","sequence":"additional","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"},{"name":"Hospital da Luz Learning Health, Luz Sa\u00fade, 1500-650 Lisboa, Portugal"}]},{"given":"Catarina","family":"Fidalgo","sequence":"additional","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"},{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"}]},{"given":"Lu\u00eds","family":"Mascarenhas-Lemos","sequence":"additional","affiliation":[{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"},{"name":"NOVA Medical School, 1169-056 Lisboa, Portugal"},{"name":"Catolica Medical School, 1649-023 Lisboa, Portugal"}]},{"given":"Maria Pia","family":"Costa-Santos","sequence":"additional","affiliation":[{"name":"Hospital do Divino Esp\u00edrito Santo, 9500-370 Ponta Delgada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9971-212X","authenticated-orcid":false,"given":"Rui","family":"Maio","sequence":"additional","affiliation":[{"name":"Hospital Beatriz \u00c2ngelo, 2674-514 Loures, Portugal"},{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"},{"name":"NOVA Medical School, 1169-056 Lisboa, Portugal"}]},{"given":"Jorge","family":"Paulino","sequence":"additional","affiliation":[{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"},{"name":"NOVA Medical School, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5255-7095","authenticated-orcid":false,"given":"Pedro","family":"Viana Baptista","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-4438","authenticated-orcid":false,"given":"Alexandra R.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"given":"Mar\u00edlia","family":"Cravo","sequence":"additional","affiliation":[{"name":"Hospital da Luz, 1500-650 Lisboa, Portugal"},{"name":"Lisbon School of Medicine, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S2468-1253(19)30347-4","article-title":"The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"4","author":"Pourshams","year":"2019","journal-title":"Lancet Gastroenterol. 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