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

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 PDACÀCP discrimination that could accelerate treatment and improve its dismal prognosis.

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

“…However, CA19-9 also gives false positive results in benign pancreaticobiliary diseases [ 14 , 15 ]. Several studies reported a number of non-invasive diagnostic and/or prognostic markers of pancreatic cancer that have been tested alone or in combination, such as: CA125, CEA, CEACAM1, MUC1, MIC1/GDF15, REG3A/PAP1, PKM2 and AXL, as well as auto-antibodies, fecal microbiome signatures and myeloid-derived suppressor cells [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Yet, the clinical utility of these markers remains to be determined.…”

Activated AXL Protects Against Hepatic Ischemia-reperfusion Injury by Upregulating SOCS-1 Expression

“…Therefore, targeting AXL therapy may be a novel therapeutic strategy to prevent and treat hepatic I/R injury. Although soluble AXL is considered to be a possible serum biomarker for chronic pancreatitis, liver fibrosis, and liver cirrhosis, 36 , 37 whether sAXL can become a novel serum biomarker for the degree of hepatic I/R injury needs to be further clarified.…”

Dissecting the Role of AXL in Cancer Immune Escape and Resistance to Immune Checkpoint Inhibition

“…Some studies have reported AXL as an independent prognostic marker ( 56 , 62 , 68 , 70 , 72 , 73 , 78 , 82 , 83 , 87 , 90 – 92 ). Moreover, soluble forms of AXL resulting from shedding of the receptor have been characterized, with potential utility for patient monitoring in certain malignancies ( 73 , 93 – 96 ).…”