Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma

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dc.contributor.authorGonzález Borja, Iranzu
dc.contributor.authorViúdez, Antonio
dc.contributor.authorAlors-Pérez, Emilia
dc.contributor.authorGoñi Irigoyen, Saioa
dc.contributor.authorAmat Villegas, Irene
dc.contributor.authorGhanem, Ismael
dc.contributor.authorPazo-Cid, Roberto
dc.contributor.authorFeliu, Jaime
dc.contributor.authorAlonso, Laura
dc.contributor.authorLópez López, Carlos
dc.contributor.authorArrazubi, Virginia
dc.contributor.authorGallego, Javier
dc.contributor.authorPérez Sanz, Jairo
dc.contributor.authorHernández García, Irene
dc.contributor.authorVera García, Ruth
dc.contributor.authorCastaño, Justo P.
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2023-04-24T09:54:38Z
dc.date.available2023-04-24T09:54:38Z
dc.date.issued2022
dc.date.updated2023-04-24T08:17:39Z
dc.description.abstractDespite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CKβ8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.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 A.V. I.G.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. Work by JPC received funds from Spanish Ministry of Economy (MINECO; BFU2016–80360-R) and Ministry of Science and Innovation (MICINN; PID2019-105201RB-I00), Junta de Andalucía (BIO- 0139), Universidad de Córdoba-FEDER (UCO-202099901918904), GETNE2019 Research grant; and CIBERobn Fisiopatología de la Obesidad y Nutrición (CIBER is an initiative of Instituto de Salud Carlos III, co-funded by European Union: ERDF/ESF, “Investing in your future”). EAP was funded by a Predoctoral contract FI17/00282 Instituto de Salud Carlos III.en
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dc.format.mimetypeapplication/zipen
dc.identifier.citationGonzález-Borja, I., Viúdez, A., Alors-Pérez, E., Goñ,i S., Amat, I., Ghanem, I., Pazo-Cid, R., Feliu, J., Alonso, L., López, C., Arrazubi, V., Gallego, J., Pérez-Sanz, J., Hernández-García, I., Vera, R., Castaño, J.P Fernández-Irigoyen, J. (2022) Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma. Cancers, 14(23), 1-18. https://doi.org/10.3390/cancers14235993.en
dc.identifier.doi10.3390/cancers14235993
dc.identifier.issn2072-6694
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/45148
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofCancers, 2022, 14(23), 1-18en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016–80360/
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.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//008-2018/
dc.relation.publisherversionhttps://doi.org/10.3390/cancers14235993
dc.rights© 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectB lymphocytesen
dc.subjectBiomarkersen
dc.subjectBorderline diseaseen
dc.subjectCytokines and growth factorsen
dc.subjectFlow cytometry and immunohistochemistryen
dc.subjectPancreatic ductal adenocarcinoma (PDAC)en
dc.subjectProtein arraysen
dc.subjectResectable diseaseen
dc.subjectT lymphocytesen
dc.titleCytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinomaen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication7945ddd5-cf8b-4927-bd7a-4ade2fb61f11
relation.isAuthorOfPublicationee6367c6-ca22-49b5-a39e-470306c950a4
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublication.latestForDiscovery7945ddd5-cf8b-4927-bd7a-4ade2fb61f11

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