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

Authors Yang Y, Wang D, Jin L, Wu G, Bai Z, Wang J, Yao H, Zhang Z

Received 29 March 2018

Accepted for publication 9 July 2018

Published 26 September 2018 Volume 2018:10 Pages 3911—3929


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Kenan Onel

Yingchi Yang, Dong Wang, Lan Jin, Guocong Wu, Zhigang Bai, Jin Wang, Hongwei Yao, Zhongtao Zhang

Department of General Surgery, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China

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.

Keywords: meta-analysis, microsatellite instability, colorectal cancer, BRAF mutation, prognosis

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