BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer.
A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in two other cohorts (GSE 17538, GSE 14333).
The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation signature was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.019 median, 37.310 vs. 134.860 months), and disease-free survival in GSE 17538 (BRAF mutation vs. wild, P = 0.027, median 36.9 months vs. not reached). In a multivariate analysis, BRAF mutation signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.1; 95% CI 1.43-2.62: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition is the possible explanation for poor prognosis of BRAF mutation colorectal cancer.
BRAF mutation signature is highly associated with poor prognosis in colorectal cancer and the molecules associated with epithelial-mesenchymal transition can be potential treatment targets in BRAF mutation colorectal cancer.
Clinical trial identification
Legal entity responsible for the study
Chonnam National University Hwasun Hospital
All authors have declared no conflicts of interest.