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| Página principal > Artículos > Artículos publicados > Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis |
(Institut Hospital del Mar d'Investigacions Mèdiques) (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques) (Hospital Clínic i Provincial de Barcelona) (Hospital del Mar (Barcelona, Catalunya)) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques de Barcelona) (Institut d'Investigacions Biomèdiques de Barcelona)
| Fecha: | 2021 |
| Resumen: | 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. |
| Ayudas: | Ministerio de Ciencia e Innovación PI20-00625 Ministerio de Ciencia e Innovación RTI2018-095672-BI00 Ministerio de Ciencia e Innovación PI20-01696 Ministerio de Ciencia e Innovación PI18-01034 Instituto de Salud Carlos III PT20-00023 Ministerio de Economía y Competitividad RED2018-102799-T Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-225 |
| Derechos: | Aquest 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.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | 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 |
| Publicado en: | EBioMedicine, Vol. 75 (december 2021) , ISSN 2352-3964 |
