TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• TAM receptor tyrosine kinases (TYRO3, AXL, MERTK) are implicated in metastatic colorectal cancer (CRC).
• Understanding TAM receptor interactions with the central nervous system is crucial for addressing brain metastases from colorectal cancer (BM-CRC).

Purpose of the Study:

• To analyze TAM receptor expression in BM-CRC.
• To investigate the prognostic significance of TAM receptors and their ligands in metastatic CRC.

Main Methods:

• Analysis of TAM receptor expression (RNA and protein) in BM-SC-CRC cell lines, a local BM-CRC patient cohort, and TCGA metastatic CRC cohort.
• Orthotopic injection of BM-SC-CRC into mice.
• Protein expression analysis in primary tumors, brain metastases, and other metastatic sites.

Main Results:

• AXL and TYRO3 proteins were expressed across primary and metastatic sites in BM-CRC patients, with AXL showing stable or increased expression from primary to brain metastases.
• While TAM receptors and PROS1 were not prognostic in a TCGA cohort, GAS6 showed prognostic value.
• An exploratory analysis indicated poorer prognosis in patients with low AXL and high GAS6.

Conclusions:

• The TAM receptor ligand GAS6 and the AXL/GAS6 ratio may serve as prognostic markers for metastatic CRC, including BM-CRC.
• Further validation is required to confirm the prognostic impact of TAM receptors in BM-CRC.