J Cancer 2019; 10(10):2332-2341. doi:10.7150/jca.30789 This issue
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.
*These authors contributed equally to this work.
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.
Keywords: colorectal cancer, BRAF mutation, prognosis, meta-analysis