Mps1 is associated with the BRAF(V600E) mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma

摘要

In previous studies, the B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation has been identified in multiple malignant tumors. BRAF(V600E) has been revealed to contribute to tumorigenesis by the activation of phospho-mitogen-activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho-MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction-direct sequencing. It was revealed that BRAF(V600E) was present in similar to 34% of thyroid cancer cases and was associated with age, clinical tumor stage and lymph node stage. However, the association of BRAF(V600E) with overall survival was not statistically significant. The expression of Mps1 was significantly increased in tumor tissues with BRAF(V600E), however, this did not affect the expression of phospho-MAPK in thyroid carcinomas. Collectively, the results of the present study suggested that BRAF(V600E) may regulate the expression of Mps1 in MAP kinase independent ways in thyroid carcinoma. Therefore, Mps1 expression is associated with BRAF(V600E) while the upstream signaling of phospho-MAPK has no relevance. The specific mechanisms of BRAF(V600E) and the unknown pathway associated with Mps1 exhibit potential for further study, and provide a theoretical basis for the molecular treatment of thyroid carcinoma.