Clinicopathological Significance of BRAF^V600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Abstract

Background and Aims: Numerous studies have identified BRAF V600E mutation as a predictive factor of anti-EGFR antibodies in colorectal cancer (CRC). However, the association between BRAF V600E 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 BRAF V600E mutation and clinicopathological features in CRC patients. Odds ratio with 95% confidence interval were used to estimate the effects of BRAF V600E 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 BRAF V600E mutation rate was 11.38%, and BRAF V600E 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 BRAF V600E mutation was related to poor prognosis of CRC and associated with the distinct molecular phenotypes.

Prevalence of the Braf P.V600E Variant in Patients with Colorectal Cancer from Mexico and Its Estimated Frequency in Latin American and Caribbean Populations

“…The four patients bearing the p.V600E variant were three women and a man, all older than 60 years, with tumors located in the proximal colon, three of which were at stages III–IV. Although no statistical approach was possible due to the low number of patients positive for the pathogenic variant, the characteristics of these subjects are in agreement with the clinicopathological features associated with BRAF p.V600E described in three meta-analyses 12–14. Chen et al 12 reported an analysis of 25 studies, published before 2013, and estimated a frequency of this pathogenic variant of 10.8% among 11,955 patients with CRC.…”

BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights

“…In fact, as emerged in a recent meta-analysis [14], BRAF V600E-mutated tumors more commonly arise from serrated adenomas, mainly in the right colon, with a higher incidence in women and elderly patients (age >60-years-old). Moreover, BRAF V600E-mutated CRCs are often poorly differentiated and present a mucinous histotype.…”

BRAF V600E mutated metastatic colorectal cancer: current progress and future directions

“…Molecular profiling for various mutations, namely BRAF and RAS, as well as for microsatellite instability (MSI) is critical for treatment decisions. In particular, the presence of the BRAF V600E mutation, which is seen in approximately 10% of mCRC, is associated with a worse prognosis [3]. BRAF V600E mut mCRC exhibits unique clinicopathological features including older age and higher stage at diagnosis, predilection for females, right-sided tumor location, poor differentiation, and MSI-high phenotype [3,4].…”