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

Despite 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 resea...

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Autores: González-Borja, Iranzu, Viúdez, Antonio, Alors-Pérez, Emilia, Goñi, Saioa, Amat, Irene, Ghanem, Ismael, Pazo-Cid, Roberto, Feliu, Jaimen, Alonso, Laura, López López, Carlos|||0000-0002-8901-741X, Arrazubi, Virginia, Gallego, Javier, Pérez-Sanz, Jairo, Hernández-García, Irene, Vera, Ruth, Castaño, Justo P., Fernández-Irigoyen, Joaquín
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/27860
Acceso en línea:https://hdl.handle.net/10902/27860
Access Level:acceso abierto
Palabra clave:Pancreatic ductal adenocarcinoma (PDAC)
Biomarkers
Resectable disease
Borderline disease
Cytokines and growth factors
T lymphocytes
B lymphocytes
Protein arrays
Flow cytometry and immunohistochemistry
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dc.title.none.fl_str_mv Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
title Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
spellingShingle Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
González-Borja, Iranzu
Pancreatic ductal adenocarcinoma (PDAC)
Biomarkers
Resectable disease
Borderline disease
Cytokines and growth factors
T lymphocytes
B lymphocytes
Protein arrays
Flow cytometry and immunohistochemistry
title_short Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
title_full Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
title_fullStr Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
title_full_unstemmed Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
title_sort Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinoma
dc.creator.none.fl_str_mv González-Borja, Iranzu
Viúdez, Antonio
Alors-Pérez, Emilia
Goñi, Saioa
Amat, Irene
Ghanem, Ismael
Pazo-Cid, Roberto
Feliu, Jaimen
Alonso, Laura
López López, Carlos|||0000-0002-8901-741X
Arrazubi, Virginia
Gallego, Javier
Pérez-Sanz, Jairo
Hernández-García, Irene
Vera, Ruth
Castaño, Justo P.
Fernández-Irigoyen, Joaquín
López López, Carlos|||0000-0002-8901-741X
author González-Borja, Iranzu
author_facet González-Borja, Iranzu
Viúdez, Antonio
Alors-Pérez, Emilia
Goñi, Saioa
Amat, Irene
Ghanem, Ismael
Pazo-Cid, Roberto
Feliu, Jaimen
Alonso, Laura
López López, Carlos|||0000-0002-8901-741X
Arrazubi, Virginia
Gallego, Javier
Pérez-Sanz, Jairo
Hernández-García, Irene
Vera, Ruth
Castaño, Justo P.
Fernández-Irigoyen, Joaquín
author_role author
author2 Viúdez, Antonio
Alors-Pérez, Emilia
Goñi, Saioa
Amat, Irene
Ghanem, Ismael
Pazo-Cid, Roberto
Feliu, Jaimen
Alonso, Laura
López López, Carlos|||0000-0002-8901-741X
Arrazubi, Virginia
Gallego, Javier
Pérez-Sanz, Jairo
Hernández-García, Irene
Vera, Ruth
Castaño, Justo P.
Fernández-Irigoyen, Joaquín
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Pancreatic ductal adenocarcinoma (PDAC)
Biomarkers
Resectable disease
Borderline disease
Cytokines and growth factors
T lymphocytes
B lymphocytes
Protein arrays
Flow cytometry and immunohistochemistry
topic Pancreatic ductal adenocarcinoma (PDAC)
Biomarkers
Resectable disease
Borderline disease
Cytokines and growth factors
T lymphocytes
B lymphocytes
Protein arrays
Flow cytometry and immunohistochemistry
description Despite 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-12-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/27860
url https://hdl.handle.net/10902/27860
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers, 2022, 14, 5993
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Cytokines and lymphoid populations as potential biomarkers in locally and borderline pancreatic adenocarcinomaGonzález-Borja, IranzuViúdez, AntonioAlors-Pérez, EmiliaGoñi, SaioaAmat, IreneGhanem, IsmaelPazo-Cid, RobertoFeliu, JaimenAlonso, LauraLópez López, Carlos|||0000-0002-8901-741XArrazubi, VirginiaGallego, JavierPérez-Sanz, JairoHernández-García, IreneVera, RuthCastaño, Justo P.Fernández-Irigoyen, JoaquínLópez López, Carlos|||0000-0002-8901-741XPancreatic ductal adenocarcinoma (PDAC)BiomarkersResectable diseaseBorderline diseaseCytokines and growth factorsT lymphocytesB lymphocytesProtein arraysFlow cytometry and immunohistochemistryDespite 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.This 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.MDPIUniversidad de Cantabria20222022-12-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/27860Cancers, 2022, 14, 5993reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/278602026-06-02T12:39:31Z
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