Date of Award
Master of Science
AXL, a receptor tyrosine kinase, is known to promote malignant phenotypes in various types of cancer. AXL overexpression is commonly observed in glioblastoma and correlates with a worse prognosis. Detectable in most biological fluids, the extracellular domain of AXL, sAXL, is the product of enzymatic cleavage by ADAM10/17. Here we used ELISA, BCA and BCG assays to characterize blood serum from 23 newly diagnosed GBM patients which was collected roughly 24 hours before and after surgery as well as every three months post-surgery, corresponding to follow-up treatment visits. Immunoblotting was used to determine relative AXL expression in 13 patient tumor tissue samples. Additionally, T-1 weighted MRI scans were used to interpolate pre-operative tumor volume in all participating patients. Here we report that sAXL was elevated in the 84 GBM samples compared to the 40 control samples (p = 0.013). Normalizing sAXL values against corresponding serum albumin concentrations further defined the distinction between the two groups (p < 0.0001). While in the 19 paired, pre- and post- operative samples, sAXL did not respond significantly to surgical intervention, normalizing the values against albumin showed a significant elevation in response to surgery (p = 0.013). In patients whose pre-operative samples presented with sAXL elevated compared to the healthy control average (30.16 ng/mL), there was a strong positive correlation between sAXL and AXL found in the corresponding tumor tissue. Though sAXL shed from brain tumors is detectable in the serum of GBM patients, in this small series of patients, it does not correlate with tumor volume.
Raymond, Daniel, "EVALUATING SOLUBLE AXL AS A BIOMARKER FOR GLIOBLASTOMA" (2020). All NMU Master's Theses. 635.