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

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. AXL was analysed by immunohistochemistry...

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Autores: Martínez Bosch, Neus|||0000-0003-3596-0039, Cristóbal, Helena, Iglesias, Mar|||0000-0002-2274-4671, Gironella, Meritxell|||0000-0003-4437-5181, Barranco, Luis E, Visa, Laura|||0000-0002-3409-8857, Calafato, Domenico|||0000-0002-9636-9819, Jiménez-Parrado, Silvia, Earl, Julie, Carrato, Alfredo|||0000-0001-7749-8140, Manero-Rupérez, Noemí, Moreno Merino, Mireia|||0000-0001-9575-5112, Morales, Albert|||0000-0001-8702-2269, Guerra, Carmen, Navarro, Pilar|||0000-0003-4314-4584, García de Frutos, Pablo|||0000-0003-1547-1190
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:250893
Acceso en línea:https://ddd.uab.cat/record/250893
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2021.103797
Access Level:acceso abierto
Palabra clave:PDAC, Pancreatic ductal adenocarcinoma
Saxl, Soluble AXL
CP, Chronic pancreatitis
CA19-9, Carbohydrate antigen 19-9
RTKs, Receptor tyrosine kinases
PanINs, Pancreatic intraepithelial neoplasias
IPMNs, Intraductal papillary mucinous neoplasms
ROC, Receiver operating curve
AUC, Area under the curve
IQR, Interquartile range
IHC, Immunohistochemistry
FDA, Food and drug administration
GAS6, Growth arrest-specific factor 6
TCGA, The Cancer Genome Atlas
GTEx, Genotype-tissue expression
HCC, Hepatocellular carcinoma
PDAC
AXL
Pancreas
Biomarker
Differential diagnosis
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oai_identifier_str oai:ddd.uab.cat:250893
network_acronym_str ES
network_name_str España
repository_id_str
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|||0000-0003-3596-0039
PDAC, Pancreatic ductal adenocarcinoma
Saxl, Soluble AXL
CP, Chronic pancreatitis
CA19-9, Carbohydrate antigen 19-9
RTKs, Receptor tyrosine kinases
PanINs, Pancreatic intraepithelial neoplasias
IPMNs, Intraductal papillary mucinous neoplasms
ROC, Receiver operating curve
AUC, Area under the curve
IQR, Interquartile range
IHC, Immunohistochemistry
FDA, Food and drug administration
GAS6, Growth arrest-specific factor 6
TCGA, The Cancer Genome Atlas
GTEx, Genotype-tissue expression
HCC, Hepatocellular carcinoma
PDAC
AXL
Pancreas
Biomarker
Differential diagnosis
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|||0000-0003-3596-0039
Cristóbal, Helena
Iglesias, Mar|||0000-0002-2274-4671
Gironella, Meritxell|||0000-0003-4437-5181
Barranco, Luis E
Visa, Laura|||0000-0002-3409-8857
Calafato, Domenico|||0000-0002-9636-9819
Jiménez-Parrado, Silvia
Earl, Julie
Carrato, Alfredo|||0000-0001-7749-8140
Manero-Rupérez, Noemí
Moreno Merino, Mireia|||0000-0001-9575-5112
Morales, Albert|||0000-0001-8702-2269
Guerra, Carmen
Navarro, Pilar|||0000-0003-4314-4584
García de Frutos, Pablo|||0000-0003-1547-1190
author Martínez Bosch, Neus|||0000-0003-3596-0039
author_facet Martínez Bosch, Neus|||0000-0003-3596-0039
Cristóbal, Helena
Iglesias, Mar|||0000-0002-2274-4671
Gironella, Meritxell|||0000-0003-4437-5181
Barranco, Luis E
Visa, Laura|||0000-0002-3409-8857
Calafato, Domenico|||0000-0002-9636-9819
Jiménez-Parrado, Silvia
Earl, Julie
Carrato, Alfredo|||0000-0001-7749-8140
Manero-Rupérez, Noemí
Moreno Merino, Mireia|||0000-0001-9575-5112
Morales, Albert|||0000-0001-8702-2269
Guerra, Carmen
Navarro, Pilar|||0000-0003-4314-4584
García de Frutos, Pablo|||0000-0003-1547-1190
author_role author
author2 Cristóbal, Helena
Iglesias, Mar|||0000-0002-2274-4671
Gironella, Meritxell|||0000-0003-4437-5181
Barranco, Luis E
Visa, Laura|||0000-0002-3409-8857
Calafato, Domenico|||0000-0002-9636-9819
Jiménez-Parrado, Silvia
Earl, Julie
Carrato, Alfredo|||0000-0001-7749-8140
Manero-Rupérez, Noemí
Moreno Merino, Mireia|||0000-0001-9575-5112
Morales, Albert|||0000-0001-8702-2269
Guerra, Carmen
Navarro, Pilar|||0000-0003-4314-4584
García de Frutos, Pablo|||0000-0003-1547-1190
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PDAC, Pancreatic ductal adenocarcinoma
Saxl, Soluble AXL
CP, Chronic pancreatitis
CA19-9, Carbohydrate antigen 19-9
RTKs, Receptor tyrosine kinases
PanINs, Pancreatic intraepithelial neoplasias
IPMNs, Intraductal papillary mucinous neoplasms
ROC, Receiver operating curve
AUC, Area under the curve
IQR, Interquartile range
IHC, Immunohistochemistry
FDA, Food and drug administration
GAS6, Growth arrest-specific factor 6
TCGA, The Cancer Genome Atlas
GTEx, Genotype-tissue expression
HCC, Hepatocellular carcinoma
PDAC
AXL
Pancreas
Biomarker
Differential diagnosis
topic PDAC, Pancreatic ductal adenocarcinoma
Saxl, Soluble AXL
CP, Chronic pancreatitis
CA19-9, Carbohydrate antigen 19-9
RTKs, Receptor tyrosine kinases
PanINs, Pancreatic intraepithelial neoplasias
IPMNs, Intraductal papillary mucinous neoplasms
ROC, Receiver operating curve
AUC, Area under the curve
IQR, Interquartile range
IHC, Immunohistochemistry
FDA, Food and drug administration
GAS6, Growth arrest-specific factor 6
TCGA, The Cancer Genome Atlas
GTEx, Genotype-tissue expression
HCC, Hepatocellular carcinoma
PDAC
AXL
Pancreas
Biomarker
Differential diagnosis
description 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. 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. 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. sAXL appears as a biomarker for early detection of PDAC and PDAC-CP discrimination that could accelerate treatment and improve its dismal prognosis.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/250893
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2021.103797
url https://ddd.uab.cat/record/250893
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2021.103797
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI20-00625
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RTI2018-095672-BI00
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI20-01696
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI18-01034
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT20-00023
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RED2018-102799-T
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-225
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/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
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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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, Neus|||0000-0003-3596-0039Cristóbal, HelenaIglesias, Mar|||0000-0002-2274-4671Gironella, Meritxell|||0000-0003-4437-5181Barranco, Luis EVisa, Laura|||0000-0002-3409-8857Calafato, Domenico|||0000-0002-9636-9819Jiménez-Parrado, SilviaEarl, JulieCarrato, Alfredo|||0000-0001-7749-8140Manero-Rupérez, NoemíMoreno Merino, Mireia|||0000-0001-9575-5112Morales, Albert|||0000-0001-8702-2269Guerra, CarmenNavarro, Pilar|||0000-0003-4314-4584García de Frutos, Pablo|||0000-0003-1547-1190PDAC, Pancreatic ductal adenocarcinomaSaxl, Soluble AXLCP, Chronic pancreatitisCA19-9, Carbohydrate antigen 19-9RTKs, Receptor tyrosine kinasesPanINs, Pancreatic intraepithelial neoplasiasIPMNs, Intraductal papillary mucinous neoplasmsROC, Receiver operating curveAUC, Area under the curveIQR, Interquartile rangeIHC, ImmunohistochemistryFDA, Food and drug administrationGAS6, Growth arrest-specific factor 6TCGA, The Cancer Genome AtlasGTEx, Genotype-tissue expressionHCC, Hepatocellular carcinomaPDACAXLPancreasBiomarkerDifferential diagnosisEarly 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. 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. 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. sAXL appears as a biomarker for early detection of PDAC and PDAC-CP discrimination that could accelerate treatment and improve its dismal prognosis. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/250893https://dx.doi.org/urn:doi:10.1016/j.ebiom.2021.103797reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI20-00625Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RTI2018-095672-BI00Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI20-01696Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI18-01034Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT20-00023Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RED2018-102799-TAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-225open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2508932026-06-06T12:50:31Z
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