Dataset Information

Prognostic value of the combination of microsatellite instability and BRAF mutation in colorectal cancer.

ABSTRACT: Purpose:The aim of this study was to investigate the prognostic value of the combination of microsatellite instability (MSI) and BRAF V600E mutation in colorectal cancer (CRC). Materials and methods:We compare the prognosis difference among CRC patients with four subtypes according to MSI and BRAF mutation, ie, microsatellite stable/BRAF wild type (MSS/BRAFwt), MSS/BRAF mutation (MSS/BRAFmut), MSI/BRAFwt, and MSI/BRAFmut, by pooling the previous related reports and public available data sets till December 2017 for the first time. Results:Twenty-seven independent studies comprising 24,067 CRC patients were included. Meta-analysis suggested that, compared with MSS/BRAFwt subtype, MSS/BRAFmut was associated with shorter overall survival (OS) (N=25, HR = 2.018, 95% CI = 1.706-2.388, P=2.220E-16), while there was a trend of association of MSI/BRAFmut with OS (N=13, HR = 1.324, 95% CI = 0.938-1.868, P=1.096E-01) and no association of MSI/BRAFwt with OS (N=17, HR = 0.996, 95% CI = 0.801-1.240, P=9.761E-01). Compared with MSI/ BRAFwt subtype, MSI/BRAFmut was a poor factor for OS (N=22, HR = 1.470, 95% CI = 1.243-1.740, P=7.122E-06). Compared with MSS/BRAFmut subtype, both MSI/BRAFwt (N=11, HR = 0.560, 95% CI = 0.433-0.725, P=1.034E-05) and MSI/BRAFmut (N=16, HR = 0.741, 95% CI = 0.567-0.968, P=2.781E-02) were favorable for OS. Subgroup analysis revealed similar results in all subgroups except the subgroup of stage IV cancer, in which MSI showed poor effects on OS in BRAF wild-type patients (N=6, HR = 1.493, 95% CI = 1.187-1.879, P=6.262E-04) but not in BRAF-mutated patients (N=5, HR = 1.143, 95% CI = 0.789-1.655, P=4.839E-01). Meta-analysis regression and test of interaction revealed no interaction of MSI with BRAF mutation when evaluating the associations of MSI/BRAF mutation subtypes with OS in CRC. Conclusion:Among the four subtypes according to MSI and BRAF mutation, MSS/BRAFmut was a poor prognostic factor, while MSS/BRAFwt and MSI/BRAFwt were comparable and favorable and MSI/BRAFmut was moderate in CRC. The combination of MSI/BRAF mutations could facilitate the planning of individualized treatment strategies and prognosis improvement in CRC.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6165775 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Prognostic value of the combination of microsatellite instability and <i>BRAF</i> mutation in colorectal cancer.

Yang Yingchi Y Wang Dong D Jin Lan L Wu Guocong G Bai Zhigang Z Wang Jin J Yao Hongwei H Zhang Zhongtao Z

Cancer management and research 20180926

<h4>Purpose</h4>The aim of this study was to investigate the prognostic value of the combination of microsatellite instability (MSI) and <i>BRAF</i> V600E mutation in colorectal cancer (CRC).<h4>Materials and methods</h4>We compare the prognosis difference among CRC patients with four subtypes according to MSI and <i>BRAF</i> mutation, ie, microsatellite stable/<i>BRAF</i> wild type (MSS/<i>BRAF</i>wt), MSS/<i>BRAF</i> mutation (MSS/<i>BRAF</i>mut), MSI/<i>BRAF</i>wt, and MSI/<i>BRAF</i>mut, by ...[more]

PMID: 30310312

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Project description:The BRAF (V600E) mutation in colorectal cancers that are microsatellite stable (MSS) confers a poor patient prognosis, whereas BRAF mutant microsatellite-unstable (MSI) colorectal cancers have an excellent prognosis. BRAF wild type cancers are typically MSS and display chromosomal instability (CIN). CIN has not been extensively studied on a genome-wide basis in relation to BRAF mutational status in colorectal cancer. BRAF mutant/MSS (BRAFmut/MSS) cancers (n = 33) and BRAF mutant/MSI (BRAFmut/MSI) cancers (n = 30) were compared for presence of copy number aberrations (CNAs) indicative of CIN, with BRAF wild type/MSS (BRAFwt/MSS) cancers (n = 18) using Illumina CytoSNP-12 arrays. BRAFmut/MSS and BRAFwt/MSS cancers showed comparable numbers of CNAs/cancer at 32.8 and 29.8 respectively. However, there were differences in patterns of CNA length between MSS cohorts, with BRAFmut/MSS cancers having significantly greater proportions of focal CNAs compared to BRAFwt/MSS cancers (p<0.0001); whereas whole chromosomal arm CNAs were more common in BRAFwt/MSS cancers (p<0.0001). This related to a reduced average CNA length in BRAFmut/MSS compared to BRAFwt/MSS cancers (20.7 Mb vs 33.4 Mb;p<0.0001); and a smaller average percent of CIN affected genomes in BRAFmut/MSS compared to BRAFwt/MSS cancers (23.9% vs 34.9% respectively). BRAFmut/MSI cancers were confirmed to have low CNA rates (5.4/cancer) and minimal CIN-affected genomes (average of 4.5%) compared to MSS cohorts (p<0.0001). BRAFmut/MSS cancers had more frequent deletion CNAs compared to BRAFwt/MSS cancers on 6p and 17q at loci not typically correlated with colorectal cancer, and greater amplification CNAs on 8q and 18q compared to BRAFwt/MSS cancers. These results indicate that comparable rates of CIN occur between MSS subgroups, however significant differences in their patterns of instability exist, with BRAFmut/MSS cancers showing a 'focal pattern' and BRAFwt/MSS cancers having a 'whole arm pattern' of CIN. This and the genomic loci more frequently affected in BRAFmut/MSS cancers provides further evidence of the biological distinctions of this important cancer subgroup.

Dataset Information

Prognostic value of the combination of microsatellite instability and BRAF mutation in colorectal cancer.

Publications

Prognostic value of the combination of microsatellite instability and <i>BRAF</i> mutation in colorectal cancer.

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