Clinicopathological significance of BRAFV600E mutation in colorectal cancer: An updated meta-analysis

Abstract

Background and Aims: Numerous studies have identified BRAFV600E mutation as a predictive factor of anti-EGFR antibodies in colorectal cancer (CRC). However, the association between BRAFV600E mutation and clinicopathological features remains unclear. Therefore, we aimed to conduct an updated and comprehensive meta-analysis to evaluate the above issues. Methods: We performed a systematic literature search from PubMed, Web of Science, Embase, and PMC database examining the association between BRAFV600E mutation and clinicopathological features in CRC patients. Odds ratio with 95% confidence interval were used to estimate the effects of BRAFV600E mutation on each clinicopathological parameter with fixed-effect model or random-effect model. Results: Sixty-one studies published, including 32407 CRC patients from multiple countries, were included in the meta-analysis. The overall BRAFV600E mutation rate was 11.38%, and BRAFV600E mutation was positively related to high disease stage (OR=0.81; 95% CI=0.72–0.92; P=0.001), high T stage (OR=0.51; 95% CI=0.40–0.65; P<0.00001), proximal colon (OR=4.76; 95% CI=3.81–5.96; P<0.00001) or right colon (OR=5.15; 95% CI=4.35–6.10, P<0.00001) tumor location, poor tumor differentiation (OR=0.27; 95% CI=0.21–0.34; P<0.00001), mucinous histology (OR=2.97; 95% CI=2.37–3.72; P<0.00001), K-ras-wild type (OR=0.04; 95% CI=0.02–0.07; P<0.00001), TP53-wild type (OR=0.50; 95% CI=0.31–0.78; P=0.003), deficient DNA mismatch repair (OR=2.93; 95% CI=1.78–4.82; P<0.00001), high microsatellite instability (OR=11.15; 95% CI=8.51–14.61; P<0.00001) and high CpG island methylator phenotype (OR=0.04; 95% CI=0.03–0.08; P<0.00001). Conclusions: Our updated meta-analysis demonstrated that BRAFV600E mutation was related to poor prognosis of CRC and associated with the distinct molecular phenotypes.