Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Canada.
PLoS One. 2012;7(10):e47054. doi: 10.1371/journal.pone.0047054. Epub 2012 Oct 9.
Mutation of BRAF is a predominant event in cancers with poor prognosis such as melanoma and colorectal cancer. BRAF mutation leads to a constitutive activation of mitogen activated protein kinase pathway which is essential for cell proliferation and tumor progression. Despite tremendous efforts made to target BRAF for cancer treatment, the correlation between BRAF mutation and patient survival is still a matter of controversy.
METHODS/PRINCIPAL FINDINGS: Clinical studies on the correlation between BRAF mutation and patient survival were retrieved from MEDLINE and EMBASE databases between June 2002 and December 2011. One hundred twenty relevant full text studies were categorized based on study design and cancer type. Publication bias was evaluated for each category and pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated using random or fixed effect meta-analysis based on the percentage of heterogeneity. Twenty six studies on colorectal cancer (11,773 patients) and four studies on melanoma (674 patients) were included in our final meta-analysis. The average prevalence of BRAF mutation was 9.6% in colorectal cancer, and 47.8% in melanoma reports. We found that BRAF mutation increases the risk of mortality in colorectal cancer patients for more than two times; HR = 2.25 (95% CI, 1.82-2.83). In addition, we revealed that BRAF mutation also increases the risk of mortality in melanoma patients by 1.7 times (95% CI, 1.37-2.12).
We revealed that BRAF mutation is an absolute risk factor for patient survival in colorectal cancer and melanoma.
BRAF 突变是预后不良的癌症（如黑色素瘤和结直肠癌）中的主要事件。BRAF 突变导致丝裂原活化蛋白激酶途径的组成性激活，这对于细胞增殖和肿瘤进展至关重要。尽管为癌症治疗靶向 BRAF 做出了巨大努力，但 BRAF 突变与患者生存之间的相关性仍然存在争议。
方法/主要发现：从 MEDLINE 和 EMBASE 数据库中检索了 2002 年 6 月至 2011 年 12 月之间关于 BRAF 突变与患者生存相关性的临床研究。根据研究设计和癌症类型对 120 篇相关全文研究进行了分类。对每个类别进行了发表偏倚评估，并根据异质性百分比使用随机或固定效应荟萃分析计算了合并危险比 (HR) 和 95%置信区间 (CI)。最终荟萃分析包括 26 项结直肠癌（11773 例患者）和 4 项黑色素瘤（674 例患者）研究。结直肠癌中 BRAF 突变的平均流行率为 9.6%，黑色素瘤报告中的流行率为 47.8%。我们发现 BRAF 突变使结直肠癌患者的死亡风险增加了两倍以上；HR=2.25（95%CI，1.82-2.83）。此外，我们还发现 BRAF 突变使黑色素瘤患者的死亡风险增加了 1.7 倍（95%CI，1.37-2.12）。
我们揭示了 BRAF 突变是结直肠癌和黑色素瘤患者生存的绝对风险因素。
