Deciphering CHFR role in pancreatic ductal adenocarcinoma

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dc.contributor.authorGonzález Borja, Iranzu
dc.contributor.authorAlors-Pérez, Emilia
dc.contributor.authorAmat Villegas, Irene
dc.contributor.authorAlonso, Laura
dc.contributor.authorViyuela-García, Cristina
dc.contributor.authorGoñi Irigoyen, Saioa
dc.contributor.authorReyes, José C.
dc.contributor.authorCeballos-Chávez, María
dc.contributor.authorHernández García, Irene
dc.contributor.authorSánchez-Frías, Marina E.
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorRazquin, Socorro
dc.contributor.authorArjona Sánchez, Álvaro
dc.contributor.authorArrazubi, Virginia
dc.contributor.authorPérez Sanz, Jairo
dc.contributor.authorVera García, Ruth
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorCastaño, Justo P.
dc.contributor.authorViúdez, Antonio
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-04-06T11:59:48Z
dc.date.available2022-04-06T11:59:48Z
dc.date.issued2021
dc.description.abstractCheckpoint with forkhead-associated and ring finger domains (CHFR) has been proposed as a predictive and prognosis biomarker for different tumor types, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was two-pronged: to review the role of CHFR in PDAC and evaluating CHFR as a potential predictive biomarker in this disease. For this purpose, we first explored the CHFR messenger (m)RNA expression and promoter methylation through the TCGA database. Secondly, the CHFR expression and promoter methylation were prospectively evaluated in a cohort of patients diagnosed with borderline (n = 19) or resectable (n = 16) PDAC by immunohistochemistry (IHC), methylation specific-PCR (MSP), and pyrosequencing. The results from the TCGA database showed significant differences in terms of progression-free survival (PFS) and overall survival (OS) based on the CHFR mRNA expression, which was likely independent from the promoter methylation. Importantly, our results showed that in primarily resected patients and also the entire cohort, a higher CHFR expression as indicated by the higher IHC staining intensity might identify patients with longer disease-free survival (DFS) and OS, respectively. Similarly, in the same cohorts, patients with lower methylation levels by pyrosequencing showed significantly longer OS than patients without this pattern. Both, the CHFR expression intensity and its promoter methylation were established as independent prognostic factors for PFS and OS in the entire cohort. In contrast, no significant differences were found between different methylation patterns for CHFR and the response to taxane-based neoadjuvant treatment. These results suggest the potential role of the higher expression of CHFR and the methylation pattern of its promoter as potential prognostic biomarkers in PDAC, thus warranting further comprehensive studies to extend and confirm our preliminary findings.en
dc.description.sponsorshipThis work was funded by grants from the Department of Health from the Government of Navarra (Ref. 008-2018), REFBIO II Pyrenees Biomedical Network from Programa INTERREG V-A España-Francia-Andorra (Ref. BMK_PANC) and Sociedad Española de Oncología Médica (SEOM) to AV. IG-B was supported by a predoctoral fellowship from the Department of Economic Development Government of Navarre Ayudas para la contratación de doctorandos y doctorandas por empresas y organismos de investigación y difusión de conocimientos: doctorados industriales 2018–2020. Intensification Programme Navarrabiomed 2017-2021 Obra Social La Caixa Fundación Caja Navarra. This work has also been supported by the Spanish Ministry of Economy [MINECO; BFU2016-80360-R (to JC)] and the Ministry of Science and Innovation [MICINN; PID2019-105201RB-I00 (to JC)]. Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, Investing in your future) [Predoctoral contract FI17/00282 (to EA-P)]. Junta de Andalucía (BIO-0139); GETNE2016 and GETNE2019 Research grants (to JC); and CIBERobn.en
dc.format.extent10 p.
dc.format.mimetypeapplication/pdfen
dc.identifier.doi10.3389/fmed.2021.720128
dc.identifier.issn2296-858X
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/42637
dc.language.isoengen
dc.publisherFrontiers Media
dc.relation.ispartofFrontiers in Medicine, 8
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-80360-R/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105201RB-I00/ES/
dc.relation.publisherversionhttps://doi.org/10.3389/fmed.2021.720128
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCheckpoint with forkhead and ring finger domains (CHFR)ex
dc.subjectDNA methylationen
dc.subjectImmunohistochemistry (IHC)en
dc.subjectMethylationen
dc.subjectPancreatic ductal adenocarcinoma (PDAC)en
dc.titleDeciphering CHFR role in pancreatic ductal adenocarcinomaen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationee6367c6-ca22-49b5-a39e-470306c950a4
relation.isAuthorOfPublication7945ddd5-cf8b-4927-bd7a-4ade2fb61f11
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublication.latestForDiscoveryee6367c6-ca22-49b5-a39e-470306c950a4

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