| Popis: |
AXL, a member of the TAM family of tyrosine kinases, engages cellular pathways that promote a cancer phenotype. In glioblastoma, increasing AXL expression is associated with worse prognosis. The extracellular domain of AXL is cleaved by the sheddases ADAM10 and ADAM17, releasing soluble AXL (sAXL), which is detectable in blood and tumor related fluid collections. In this study we use ELISA to measure serum sAXL levels in 23 patients with newly diagnosed GBM pre- and post- operatively and every 3 months during treatment. Relative AXL expression was assessed in tumor tissue obtained from 13 patients via western blotting. Additionally, we used T1-weighted MRI scans to interpolate pre-operative tumor volume for all patients enrolled in the study. We found that serum sAXL concentrations were elevated in 84 GBM serum samples (35.77 ±1.25 ng/mL) compared to 40 healthy volunteer samples (30.16 ±1.88 ng/mL). When normalized to total serum albumin the difference between GBM and healthy controls was statistically significant (t(df)=5.647(122), p= 0.0132). In the 19 patients with paired samples, the pre- and post- operative sAXL levels were not significantly different. Using the Pearson method, we did not find a significant correlation between tumor volume and sAXL level. However, in patients with sAXL levels above the healthy population average, there was a moderate negative correlation between sAXL and pre-operative tumor volume (r= -0.58; p= 0.23). Interestingly, there was a strong correlation between sAXL level and tumor expression of AXL in patients with high preoperative sAXL levels (r= 0.85; p= 0.03). 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. That said, we feel a larger study correlating sAXL level with improved volumetric MRI determination of viable GBM is warranted. |
