550P - Prognostic significance of BRAF mutation-associated gene signature in colorectal cancer

Abstract

Background: 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. Methods: 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). Results: 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. Conclusions: 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. Legal entity responsible for the study: Chonnam National University Hwasun Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.