Clinicopathological Significance of BRAFV600E Mutation in Colorectal Cancer: An Updated Meta-Analysis

Jianhua Wang; Jiajia Shen; Chi Huang; Meng Cao; Lizong Shen

doi:10.7150/jca.30789

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

J Cancer. 2019 May 26;10(10):2332-2341. doi: 10.7150/jca.30789. eCollection 2019.

Authors

Jianhua Wang^{1

2}, Jiajia Shen¹, Chi Huang², Meng Cao³, Lizong Shen^{1

4}

Affiliations

¹ Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
² Department of General Surgery, Affiliated Hospital of Integrated Chinese and Western Medicine of Nanjing University of Chinese Medicine, Nanjing 210028, China.
³ Lab of cellular and molecular biology, Affiliated Hospital of Integrated Chinese and Western Medicine of Nanjing University of Chinese Medicine, Nanjing 210028, China.
⁴ Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

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.

Keywords: BRAF mutation; colorectal cancer; meta-analysis; prognosis.