BRAF Mutation is Associated with an Improved Survival in Glioma-a Systematic Review and Meta-analysis

Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR = 0.60; 95% CI = 0.44-0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR = 1.39; 95% CI = 0.82-2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35 years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.