Lysyl Oxidase Is a Key Player in BRAF/MAPK Pathway-Driven Thyroid Cancer Aggressiveness

Background: The BRAFV600E mutation is the most common somatic mutation in thyroid cancer. The mechanism associated with BRAF-mutant tumor aggressiveness remains unclear. Lysyl oxidase (LOX) is highly expressed in aggressive thyroid cancers, and involved in cancer metastasis. The objective was to determine whether LOX mediates the effect of the activated MAPK pathway in thyroid cancer. Methods: The prognostic value of LOX and its association with mutated BRAF was analyzed in The Cancer Genome Atlas and an independent cohort. Inhibition of mutant BRAF and the MAPK pathway, and overexpression of mutant BRAF and mouse models of BRAFV600E were used to test the effect on LOX expression. Results: In The Cancer Genome Atlas cohort, LOX expression was higher in BRAF-mutant tumors compared to wild-type tumors (p < 0.0001). Patients with BRAF-mutant tumors with high LOX expression had a shorter disease-free survival (p = 0.03) compared to patients with a BRAF mutation and the low LOX group. In the independent cohort...