Soluble AXL, a new blood biomarker for early detection of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. Its aggressive nature, resistance to current treatments and late diagnosis make it one of the most lethal cancers in the world. Moreover, until now, there has been no specific biomarker to diagnose PDAC early and predict patient outcome.

PDAC is rarely detected in its early stages, favoring the development of metastases and decreasing the survival rate of patients. Currently only 3-5% of patients survive 5 years after diagnosis.

For this reason, there is an urgent need to study and identify new biomarkers capable of detecting the presence of PDAC in order to achieve an early diagnosis that can lead to surgical resection and increase the survival rate.

Recently, a study published in eBioMedicine by Martínez-Bosch et al. has observed a correlation between a biomarker called soluble AXL (sAXL), which is found in the blood circulation, and the early detection of PDAC. Furthermore, this marker is able to differentiate between the diagnosis of PDAC and chronic pancreatitis (CP).

To date, the only FDA (Food and Drug Administration) approved biomarker studied for the diagnosis of PDAC is carbohydrate antigen 19-9 (CA19-9). However, due to its low sensitivity and specificity, it is only used for the diagnosis of PDAC and cannot be used to study treatment response and tumor recurrence in already diagnosed patients.

In the study, two independent cohorts (Hospital del Mar [HMar] and Hospital Clínic [HClinic], Barcelona, ES) were involved, with two different groups; one with healthy individuals or control group and the other with individuals presenting with PDAC or PC.

After analyzing the levels of sAXL and GAS6 (specific ligand of AXL, which binds to circulating sAXL), the results obtained were as follows:



Adapted from Martínez-Bosch et al. eBioMedicine (2022). PDAC: Pancreatic ductal adenocarcinoma; CP: chronic pancreatitis.




Moreover, an analysis of sAXL and GAS6 expression during PDAC progression and prognosis was performed. Samples from PDAC patients were classified according to the clinical stage of the disease with the control or healthy group. Of note, PDAC is classified in 4 stages based on tumor extension, spread to adjacent lymph nodes and spread (metastasis) to distant sites.

The results of the study indicated that stages II, III and IV of the disease showed higher concentrations of sAXL compared to the control group, but no significant differences were observed between the different stages. The results obtained suggested that sAXL could be a good biomarker for the early diagnosis of PDAC because its overexpression is manifested in the early stages of the disease. A correlation between elevated levels of sAXL and GAS6 and decreased survival was also confirmed. Therefore, the presence of elevated GAS6 levels could also be a prognostic indicator in patients with PDAC.

In conclusion, these results indicate that sAXL could be the first non-invasive biomarker for the diagnosis of early-stage PDAC, thus improving the diagnosis of the disease and increasing survival in one of the most lethal cancers.



Reference

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. Epub 2021 Dec 29. PMID: 34973624; PMCID: PMC8724936.

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