Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis

Background: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. Methods: AXL was analysed by...

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Autores: Martínez Bosch, Neus, Cristóbal, Helena, Iglesias, Mar, Gironella, Meritxell, Barranco, Luis, Visa, Laura, Calafato, Domenico, Jiménez Parrado, Silvia, Earl, Julie, Carrato, Alfredo, Manero Rupérez, Noemí, Moreno, Mireia, Morales, Albert, Guerra, Carmen, Navarro, Pilar, García de Frutos, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/209231
Acceso en línea:https://hdl.handle.net/2445/209231
Access Level:acceso abierto
Palabra clave:Marcadors tumorals
Malalties del pàncrees
Tumor markers
Pancréas diseases
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spelling Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitisMartínez Bosch, NeusCristóbal, HelenaIglesias, MarGironella, MeritxellBarranco, LuisVisa, LauraCalafato, DomenicoJiménez Parrado, SilviaEarl, JulieCarrato, AlfredoManero Rupérez, NoemíMoreno, MireiaMorales, AlbertGuerra, CarmenNavarro, PilarGarcía de Frutos, PabloMarcadors tumoralsMalalties del pàncreesTumor markersPancréas diseasesBackground: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. Methods: AXL was analysed by immunohistochemistry in human pancreatic tissue samples. RNA expression analysis was performed using TCGA/GTEx databases. The plasma concentrations of sAXL, its ligand GAS6, and CA19-9 were studied in two independent cohorts, the HMar cohort (n = 59) and the HClinic cohort (n = 142), including healthy controls, chronic pancreatitis (CP) or PDAC patients, and in a familial PDAC cohort (n = 68). AXL expression and sAXL release were studied in PDAC cell lines and murine models. Findings: AXL is increased in PDAC and precursor lesions as compared to CP or controls. sAXL determined in plasma from two independent cohorts was significantly increased in the PDAC group as compared to healthy controls or CP patients. Patients with high levels of AXL have a lower overall survival. ROC analysis of the plasma levels of sAXL, GAS6, or CA19-9 in our cohorts revealed that sAXL outperformed CA19-9 for discriminating between CP and PDAC. Using both sAXL and CA19-9 increased the diagnostic value. These results were validated in murine models, showing increased sAXL specifically in animals developing PDAC but not those with precursor lesions or acinar tumours. Interpretation: sAXL appears as a biomarker for early detection of PDAC and PDAC–CP discrimination that could accelerate treatment and improve its dismal prognosis. Funding: This work was supported by grants PI20/00625 (PN), RTI2018-095672-B-I00 (AM and PGF), PI20/01696 (MG) and PI18/01034 (AC) from MICINN-FEDER and grant 2017/SGR/225 (PN) from Generalitat de Catalunya. © 2021 The Author(s)2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/209231Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2021.103797Ebiomedicine, 2022, vol. 75https://doi.org/10.1016/j.ebiom.2021.103797cc by-nc-nd (c) Martínez Bosch, Neus et al, 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2092312026-05-27T06:46:51Z
dc.title.none.fl_str_mv Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
title Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
spellingShingle Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
Martínez Bosch, Neus
Marcadors tumorals
Malalties del pàncrees
Tumor markers
Pancréas diseases
title_short Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
title_full Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
title_fullStr Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
title_full_unstemmed Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
title_sort Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
dc.creator.none.fl_str_mv Martínez Bosch, Neus
Cristóbal, Helena
Iglesias, Mar
Gironella, Meritxell
Barranco, Luis
Visa, Laura
Calafato, Domenico
Jiménez Parrado, Silvia
Earl, Julie
Carrato, Alfredo
Manero Rupérez, Noemí
Moreno, Mireia
Morales, Albert
Guerra, Carmen
Navarro, Pilar
García de Frutos, Pablo
author Martínez Bosch, Neus
author_facet Martínez Bosch, Neus
Cristóbal, Helena
Iglesias, Mar
Gironella, Meritxell
Barranco, Luis
Visa, Laura
Calafato, Domenico
Jiménez Parrado, Silvia
Earl, Julie
Carrato, Alfredo
Manero Rupérez, Noemí
Moreno, Mireia
Morales, Albert
Guerra, Carmen
Navarro, Pilar
García de Frutos, Pablo
author_role author
author2 Cristóbal, Helena
Iglesias, Mar
Gironella, Meritxell
Barranco, Luis
Visa, Laura
Calafato, Domenico
Jiménez Parrado, Silvia
Earl, Julie
Carrato, Alfredo
Manero Rupérez, Noemí
Moreno, Mireia
Morales, Albert
Guerra, Carmen
Navarro, Pilar
García de Frutos, Pablo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors tumorals
Malalties del pàncrees
Tumor markers
Pancréas diseases
topic Marcadors tumorals
Malalties del pàncrees
Tumor markers
Pancréas diseases
description Background: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. Methods: AXL was analysed by immunohistochemistry in human pancreatic tissue samples. RNA expression analysis was performed using TCGA/GTEx databases. The plasma concentrations of sAXL, its ligand GAS6, and CA19-9 were studied in two independent cohorts, the HMar cohort (n = 59) and the HClinic cohort (n = 142), including healthy controls, chronic pancreatitis (CP) or PDAC patients, and in a familial PDAC cohort (n = 68). AXL expression and sAXL release were studied in PDAC cell lines and murine models. Findings: AXL is increased in PDAC and precursor lesions as compared to CP or controls. sAXL determined in plasma from two independent cohorts was significantly increased in the PDAC group as compared to healthy controls or CP patients. Patients with high levels of AXL have a lower overall survival. ROC analysis of the plasma levels of sAXL, GAS6, or CA19-9 in our cohorts revealed that sAXL outperformed CA19-9 for discriminating between CP and PDAC. Using both sAXL and CA19-9 increased the diagnostic value. These results were validated in murine models, showing increased sAXL specifically in animals developing PDAC but not those with precursor lesions or acinar tumours. Interpretation: sAXL appears as a biomarker for early detection of PDAC and PDAC–CP discrimination that could accelerate treatment and improve its dismal prognosis. Funding: This work was supported by grants PI20/00625 (PN), RTI2018-095672-B-I00 (AM and PGF), PI20/01696 (MG) and PI18/01034 (AC) from MICINN-FEDER and grant 2017/SGR/225 (PN) from Generalitat de Catalunya. © 2021 The Author(s)
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/209231
url https://hdl.handle.net/2445/209231
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2021.103797
Ebiomedicine, 2022, vol. 75
https://doi.org/10.1016/j.ebiom.2021.103797
dc.rights.none.fl_str_mv cc by-nc-nd (c) Martínez Bosch, Neus et al, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Martínez Bosch, Neus et al, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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