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

PURPOSE

The aim of this study was to investigate the prognostic value of the combination of microsatellite instability (MSI) and V600E mutation in colorectal cancer (CRC).

MATERIALS AND METHODS

We compare the prognosis difference among CRC patients with four subtypes according to MSI and mutation, ie, microsatellite stable/ wild type (MSS/wt), MSS/ mutation (MSS/mut), MSI/wt, and MSI/mut, 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/wt subtype, MSS/mut 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/mut with OS (N=13, HR = 1.324, 95% CI = 0.938-1.868, =1.096E-01) and no association of MSI/wt with OS (N=17, HR = 0.996, 95% CI = 0.801-1.240, =9.761E-01). Compared with MSI/ wt subtype, MSI/mut was a poor factor for OS (N=22, HR = 1.470, 95% CI = 1.243-1.740, =7.122E-06). Compared with MSS/mut subtype, both MSI/wt (N=11, HR = 0.560, 95% CI = 0.433-0.725, =1.034E-05) and MSI/mut (N=16, HR = 0.741, 95% CI = 0.567-0.968, =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 wild-type patients (N=6, HR = 1.493, 95% CI = 1.187-1.879, =6.262E-04) but not in -mutated patients (N=5, HR = 1.143, 95% CI = 0.789-1.655, =4.839E-01). Meta-analysis regression and test of interaction revealed no interaction of MSI with mutation when evaluating the associations of MSI/ mutation subtypes with OS in CRC.

CONCLUSION

Among the four subtypes according to MSI and mutation, MSS/mut was a poor prognostic factor, while MSS/wt and MSI/wt were comparable and favorable and MSI/mut was moderate in CRC. The combination of MSI/ mutations could facilitate the planning of individualized treatment strategies and prognosis improvement in CRC.