Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer

摘要: Background The BRAF V600E (BRAF+) mutation activates the mitogen-activated protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC). Clinically, behavior of BRAF+ PTC, however, varies from indolent to course. SPRY2 is a negative feedback regulator MAPK/ERK pathway. We hypothesize that level expression contributes output accounts for clinical heterogeneity. Methods A tissue microarray with BRAF-positive PTCs (BRAF+ PTCs) was constructed analyzed output. Data were studied context clinicopathologic factors develop risk stratification system predictive tumor biology. function by silencing PTC cells. These cells treated inhibitors assessed growth effects. Results intact do not exhibit lymph node metastases. dysregulated pathways have nodal metastasis. When silenced, are significantly more sensitive inhibition. Conclusion likely dependent on both driver its regulatory feedback. intact, seems be less aggressive. This observation has direct important implications alter our treatment strategies.