title: BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
  
  
  METHODS
  We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model.
  
  
  RESULTS
  25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Jun-Fu
authors.initials: JF
authors.lastname: Huang
authors.affiliation: Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Zheng-Ran
authors.initials: ZR
authors.lastname: Chuai
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Da-Chuan
authors.initials: DC
authors.lastname: Shi
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Fu
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D016017:Odds Ratio; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf