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

Martínez Bosch, Neus; Cristóbal, Helena; Iglesias Coma, Mar; Gironella, Meritxell; Barranco Priego, Luis Eugenio; Visa Turmo, Laura; Calafato, Domenico; Jiménez-Parrado, Silvia; Earl, Julie; Carrato, Alfredo; Manero Rupérez, Noemí; Moreno, Mireia; Morales, Albert; Guerra, Carmen; Navarro Medrano, Pilar; García de Frutos, Pablo

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

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dc.contributor.author Martínez Bosch, Neus
dc.contributor.author Cristóbal, Helena
dc.contributor.author Iglesias Coma, Mar
dc.contributor.author Gironella, Meritxell
dc.contributor.author Barranco Priego, Luis Eugenio
dc.contributor.author Visa Turmo, Laura
dc.contributor.author Calafato, Domenico
dc.contributor.author Jiménez-Parrado, Silvia
dc.contributor.author Earl, Julie
dc.contributor.author Carrato, Alfredo
dc.contributor.author Manero Rupérez, Noemí
dc.contributor.author Moreno, Mireia
dc.contributor.author Morales, Albert
dc.contributor.author Guerra, Carmen
dc.contributor.author Navarro Medrano, Pilar
dc.contributor.author García de Frutos, Pablo
dc.date.accessioned 2022-09-15T07:15:49Z
dc.date.available 2022-09-15T07:15:49Z
dc.date.issued 2022
dc.description.abstract 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.
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN)/ Instituto de Salud Carlos III (ISCIII)-European Regional Development Fund (ERDF) ( PI20/00625 ) and the “Generalitat de Catalunya” (2017/SGR/225) to PN; grants from the MICINN (Project# RTI2018-095672-B-I00) to AM and PGdF; grant from the MICINN/ ISCIII-FEDER (PI20/01696) to MG and grant from the MICINN/ ISCIII-FEDER (PI18/01034) to AC. We also acknowledge grants from the Instituto de Salud Carlos III (ISCIII)/ ERDF( PT20/00023 ) and the "Xarxa de Bancs de tumours” sponsored by Pla Director d'Oncologia de Catalunya (XBTC). PN's lab is part of Redes de investigación (Enfermedades Metabólicas y Cáncer RED2018-102799-T), a project run by MINECO. CIBEREHD is funded by Instituto de Salud Carlos III.
dc.format.mimetype application/pdf
dc.identifier.citation Martínez-Bosch N, Cristóbal H, Iglesias M, Gironella M, Barranco L, Visa L, Calafato D, Jiménez-Parrado S, Earl J, Carrato A, Manero-Rupérez N, Moreno M, Morales A, Guerra C, Navarro P, García de Frutos P. Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis. EBioMedicine. 2022 Jan;75:103797. DOI: 10.1016/j.ebiom.2021.103797
dc.identifier.doi http://dx.doi.org/10.1016/j.ebiom.2021.103797
dc.identifier.issn 2352-3964
dc.identifier.uri http://hdl.handle.net/10230/54076
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof EBioMedicine. 2022 Jan;75:103797
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/RTI2018-095672-B-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword AXL
dc.subject.keyword Biomarker
dc.subject.keyword Differential diagnosis
dc.subject.keyword PDAC
dc.subject.keyword Pancreas
dc.title Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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