Mps1 is associated with the BRAFV600E mutation and predicts poor outcome in patients with colorectal cancer

Colorectal cancer (CRC) with the V600E mutation of B-Raf proto-oncogene serine/threonine kinase (BRAF(V600E)) mutation is insensitive to chemotherapy and is indicative of a poor patient prognosis. Although BRAF inhibitors have a marked effect on malignant melanoma harboring the BRAF(V600E) mutation, they have a limited effect on patients with CRC with the same BRAF mutation. A previous study identified a novel gene, monopolar spindle protein kinase 1 (Mps1), a downstream target of BRAF(V600E) only, rather than of wild-type BRAF as well, which contributes to tumorigenesis in melanoma. In the present study, the incidence of BRAF(V600E) in patients with CRC was identified and the correlation of Mps1, phospho-extracellular-signal-regulated kinase (p-ERK) and BRAF(V600E) was investigated. The results indicated that the mutation rate of BRAF(V600E) was 5.2% in CRC. Poorly differentiated tumors and mucinous tumors have a significantly higher incidence of BRAF(V600E) compared with well-differentiated tumors and non-mucinous tumors (P<0.05). Kaplan-Meier survival analysis indicated that the survival rate was markedly lower in patients with BRAF(V600E) compared with in patients with wild-type BRAF (BRAF(WT)). The expression of p-ERK and Mps1 in CRC with BRAF(V600E) was significantly higher compared with in CRC with BRAF(WT) (P<0.05), and their expression is associated with cancer classification, degree of differentiation and lymph node transfusion (P<0.05). In addition p-ERK expression was positively correlated with Mps1 expression, with a contingency coefficient of 0.679 (P=0.002). In conclusion, the results of the present study indicated that Mps1 was significantly associated with BRAF(V600E)/p-ERK and may serve a crucial function in the development of CRC. The results of the present study raise the possibility that targeting the oncogenic BRAF and Mps1, particularly when in conjunction, could provide promising therapeutic opportunities for the treatment of CRC.