Table 4.
Meta-analysis results for associations of MSI/BRAF mutation status with OS in colorectal cancer
| Groups | N | HR | HRlci | HRuci | PHR | Model | I2 (%) | Pheter | PBegg | PEgger |
|---|---|---|---|---|---|---|---|---|---|---|
| MSSmut/MSSwt | ||||||||||
| Overall | 25 | 2.018 | 1.706 | 2.388 | 2.220E-16 | R | 71.3 | 1.681E-08 | 2.937E-01 | 3.369E-01 |
| Cancer type | ||||||||||
| CC | 10 | 2.104 | 1.584 | 2.795 | 2.747E-07 | R | 77.6 | 6.932E-06 | ||
| MIX | 17 | 1.913 | 1.561 | 2.344 | 3.850E-10 | R | 66.7 | 4.565E-05 | ||
| Stage | ||||||||||
| I–III | 12 | 2.047 | 1.623 | 2.582 | 1.448E-09 | R | 61.9 | 2.352E-03 | ||
| IV | 8 | 2.180 | 1.844 | 2.578 | 0.000E+00 | F | 0.0 | 4.341E-01 | ||
| Therapy | ||||||||||
| S + AC | 7 | 2.000 | 1.488 | 2.687 | 4.225E-06 | R | 63.3 | 1.200E-02 | ||
| S ± AC | 21 | 2.112 | 1.701 | 2.624 | 1.380E-11 | R | 73.5 | 2.391E-08 | ||
| Chemotherapy | 4 | 1.981 | 1.606 | 2.444 | 9.963E-10 | F | 5.7% | 3.640E-01 | ||
| Sample size | ||||||||||
| <500 | 9 | 2.515 | 1.805 | 3.505 | 5.037E-08 | R | 51.2% | 3.713E-02 | ||
| 500–1,000 | 8 | 1.856 | 1.415 | 2.432 | 7.464E-06 | R | 56.5% | 2.431E-02 | ||
| >1,000 | 9 | 1.933 | 1.472 | 2.540 | 2.137E-06 | R | 82.9% | 1.681E-07 | ||
| Data resource | ||||||||||
| KM | 6 | 3.213 | 2.728 | 3.783 | 0.000E+00 | F | 20.5% | 2.790E-01 | ||
| M | 14 | 1.668 | 1.389 | 2.002 | 4.253E-08 | R | 49.2% | 1.923E-02 | ||
| U | 7 | 1.702 | 1.489 | 1.946 | 6.217E-15 | F | 15.2% | 3.144E-01 | ||
| MSIwt/MSSwt | ||||||||||
| Overall | 17 | 0.996 | 0.801 | 1.24 | 9.761E-01 | R | 69.0 | 1.247E-05 | 9.045E-01 | 3.712E-01 |
| Cancer type | ||||||||||
| CC | 6 | 0.999 | 0.677 | 1.475 | 9.970E-01 | R | 74.9 | 1.272E-03 | ||
| MIX | 12 | 1.018 | 0.785 | 1.322 | 8.887E-01 | R | 65.4 | 8.364E-04 | ||
| Stage | ||||||||||
| I–III | 6 | 0.912 | 0.589 | 1.412 | 6.818E-01 | R | 73.2 | 2.214E-03 | ||
| IV | 6 | 1.493 | 1.187 | 1.879 | 6.262E-04 | F | 40.5 | 1.350E-01 | ||
| Therapy | ||||||||||
| S + AC | 5 | 0.912 | 0.511 | 1.628 | 7.566E-01 | R | 77.5 | 1.369E-03 | ||
| S ± AC | 11 | 0.979 | 0.763 | 1.255 | 8.650E-01 | R | 57.2 | 9.493E-03 | ||
| Chemotherapy | 4 | 1.242 | 0.779 | 1.979 | 3.628E-01 | R | 53.3 | 9.246E-02 | ||
| Sample size | ||||||||||
| <500 | 5 | 1.321 | 0.981 | 1.779 | 6.577E-02 | F | 28.4 | 2.319E-01 | ||
| 500–1,000 | 4 | 0.904 | 0.669 | 1.223 | 5.157E-01 | F | 11.5 | 3.353E-01 | ||
| >1,000 | 8 | 1.023 | 0.719 | 1.456 | 8.966E-01 | R | 81.4 | 3.425E-06 | ||
| Data resource | ||||||||||
| KM | 7 | 1.388 | 1.168 | 1.650 | 1.992E-04 | F | 17.4 | 2.966E-01 | ||
| M | 7 | 0.878 | 0.614 | 1.256 | 4.777E-01 | R | 75.2 | 4.737E-04 | ||
| U | 4 | 0.742 | 0.546 | 1.008 | 5.613E-02 | F | 9.2 | 3.476E-01 | ||
| MSImut/MSSwt | ||||||||||
| Overall | 13 | 1.324 | 0.938 | 1.868 | 1.096E-01 | R | 88.2 | 2.766E-16 | 8.572E-01 | 9.922E-01 |
| Cancer type | ||||||||||
| CC | 5 | 1.289 | 0.810 | 2.051 | 2.846E-01 | R | 72.8 | 5.389E-03 | ||
| MIX | 9 | 1.346 | 0.878 | 2.064 | 1.738E-01 | R | 90.6 | 5.235E-15 | ||
| Stage | ||||||||||
| I–III | 6 | 1.623 | 0.999 | 2.637 | 5.000E-02 | R | 74.1 | 1.697E-03 | ||
| IV | 2 | 2.634 | 1.232 | 5.633 | 1.242E-02 | R | 91.8 | 4.909E-04 | ||
| Therapy | ||||||||||
| S + AC | 3 | 1.669 | 0.919 | 3.031 | 9.296E-02 | R | 66.4 | 5.079E-02 | ||
| S ± AC | 10 | 1.196 | 0.829 | 1.727 | 3.371E-01 | R | 80.5 | 5.600E-07 | ||
| Chemotherapy | 1 | 1.800 | 1.371 | 2.362 | 2.235E-05 | |||||
| Sample size | ||||||||||
| <500 | 4 | 2.551 | 1.009 | 6.447 | 4.770E-02 | R | 85.4 | 1.305E-04 | ||
| 500–1,000 | 3 | 1.185 | 0.684 | 2.055 | 5.485E-01 | R | 79.9 | 6.874E-03 | ||
| >1,000 | 6 | 1.090 | 0.715 | 1.663 | 6.892E-01 | R | 85.1 | 2.782E-06 | ||
| Data resource | ||||||||||
| KM | 8 | 1.907 | 1.255 | 2.898 | 2.528E-03 | R | 87.1 | 1.916E-09 | ||
| M | 6 | 0.849 | 0.713 | 1.010 | 6.431E-02 | F | 0.0 | 5.365E-01 | ||
| MSImut/MSIwt | ||||||||||
| Overall | 22 | 1.470 | 1.243 | 1.740 | 7.122E-06 | F | 0.0 | 3.869E-01 | 1.010E-01 | 8.788E-02 |
| Cancer type | ||||||||||
| CC | 7 | 1.554 | 1.167 | 2.070 | 2.612E-03 | F | 0.0 | 6.929E-01 | ||
| MIX | 16 | 1.401 | 1.146 | 1.712 | 1.002E-03 | F | 9.7 | 3.427E-01 | ||
| Stage | ||||||||||
| I–III | 8 | 1.599 | 1.217 | 2.101 | 7.517E-04 | F | 0.3 | 4.268E-01 | ||
| IV | 6 | 1.865 | 1.205 | 2.887 | 5.110E-03 | F | 4.9 | 3.850E-01 | ||
| Therapy | ||||||||||
| S + AC | 4 | 1.777 | 1.252 | 2.521 | 1.282E-03 | F | 0.0 | 5.766E-01 | ||
| S ± AC | 16 | 1.439 | 1.165 | 1.779 | 7.517E-04 | F | 0.0 | 5.722E-01 | ||
| Chemotherapy | 4 | 1.534 | 0.921 | 2.553 | 1.010E-01 | F | 0.0 | 5.241E-01 | ||
| Sample size | ||||||||||
| <500 | 10 | 2.207 | 1.556 | 3.129 | 8.996E-06 | F | 0.0 | 8.056E-01 | ||
| 500–1,000 | 4 | 2.013 | 1.074 | 3.770 | 2.926E-02 | F | 0.0 | 7.291E-01 | ||
| >1,000 | 8 | 1.247 | 1.003 | 1.550 | 4.659E-02 | F | 0.0 | 6.770E-01 | ||
| Data resource | ||||||||||
| KM | 8 | 1.188 | 0.915 | 1.543 | 1.971E-01 | F | 0.0 | 7.553E-01 | ||
| M | 7 | 1.548 | 1.186 | 2.022 | 1.327E-03 | F | 25.6 | 2.330E-01 | ||
| U | 8 | 1.844 | 1.303 | 2.611 | 5.606E-04 | F | 0.0 | 7.506E-01 | ||
| MSIwt/MSSmut | ||||||||||
| Overall | 11 | 0.560 | 0.433 | 0.725 | 1.034E-05 | R | 39.90 | 8.272E-02 | 5.900E-02 | 1.060E-01 |
| Cancer type | ||||||||||
| CC | 5 | 0.511 | 0.390 | 0.670 | 1.174E-06 | F | 28.7 | 2.302E-01 | ||
| MIX | 7 | 0.641 | 0.524 | 0.785 | 1.708E-05 | F | 43.60 | 1.002E-01 | ||
| Stage | ||||||||||
| I–III | 6 | 0.605 | 0.467 | 0.785 | 1.568E-04 | F | 19.0 | 2.891E-01 | ||
| IV | 3 | 0.640 | 0.510 | 0.805 | 1.281E-04 | F | 0.0 | 8.106E-01 | ||
| Therapy | ||||||||||
| S + AC | 4 | 0.624 | 0.449 | 0.867 | 4.954E-03 | F | 0.0 | 6.662E-01 | ||
| S ± AC | 10 | 0.490 | 0.343 | 0.699 | 8.148E-05 | R | 46.5 | 5.145E-02 | ||
| Chemotherapy | 1 | 0.650 | 0.510 | 0.829 | 5.205E-04 | |||||
| Sample size | ||||||||||
| <500 | 5 | 0.406 | 0.247 | 0.669 | 4.001E-04 | F | 25.0 | 2.551E-01 | ||
| >1,000 | 6 | 0.573 | 0.4 | 0.822 | 2.446E-03 | R | 49.40% | 7.841E-02 | ||
| Data resource | ||||||||||
| KM | 10 | 0.572 | 0.483 | 0.679 | 1.455E-10 | F | 25.70 | 2.072E-01 | ||
| M | 2 | 0.635 | 0.184 | 2.185 | 4.715E-01 | R | 77.6 | 3.470E-02 | ||
| MSImut/MSSmut | ||||||||||
| Overall | 16 | 0.741 | 0.567 | 0.968 | 2.781E-02 | R | 48.6 | 1.529E-02 | 8.181E-01 | 7.608E-01 |
| Cancer type | ||||||||||
| CC | 6 | 0.640 | 0.385 | 1.063 | 8.543E-02 | R | 56.1 | 4.400E-02 | ||
| MIX | 11 | 0.743 | 0.534 | 1.033 | 7.673E-02 | R | 51.6 | 2.359E-02 | ||
| Stage | ||||||||||
| I–III | 7 | 0.651 | 0.444 | 0.954 | 2.781E-02 | R | 48.9 | 6.827E-02 | ||
| IV | 5 | 1.143 | 0.789 | 1.655 | 4.839E-01 | F | 0.0 | 4.886E-01 | ||
| Therapy | ||||||||||
| S + AC | 4 | 0.918 | 0.656 | 1.284 | 6.171E-01 | F | 1.1 | 3.870E-01 | ||
| S ± AC | 11 | 0.579 | 0.408 | 0.822 | 2.213E-03 | R | 53.1 | 1.903E-02 | ||
| Chemotherapy | 4 | 1.054 | 0.676 | 1.645 | 8.181E-01 | F | 0.9 | 3.870E-01 | ||
| Sample size | ||||||||||
| <500 | 7 | 0.718 | 0.353 | 1.460 | 3.628E-01 | R | 60.5 | 1.883E-02 | ||
| 500–1,000 | 2 | 0.825 | 0.420 | 1.620 | 5.755E-01 | F | 0.0 | 3.222E-01 | ||
| >1,000 | 8 | 0.677 | 0.503 | 0.912 | 1.017E-02 | R | 54.1 | 3.293E-02 | ||
| Data resource | ||||||||||
| KM | 10 | 0.633 | 0.420 | 0.955 | 2.926E-02 | R | 58.2 | 1.057E-02 | ||
| M | 3 | 0.635 | 0.399 | 1.012 | 5.613E-02 | R | 53.9 | 1.142E-01 | ||
| U | 5 | 0.855 | 0.523 | 1.397 | 5.287E-01 | R | 53.9 | 6.990E-02 |
Note: Bold, statistically significant.
Abbreviations: AC, adjuvant chemotherapy; CC, colon cancer; M, HR was obtained from multivariate analysis; MIX, the studies included both CC and rectal cancer and results of which could not be separated; KM, HR was obtained indirectly from Kaplan–Meier plot curves; MSI, microsatellite instability; MSImut, microsatellite instability and BRAF mutation; MSIwt, microsatellite instability and BRAF wild type; MSSmut, microsatellite stable and BRAF mutation; MSSwt, microsatellite stable and BRAF wild type; RFS, recurrence free survival; S, surgery; U, HR was obtained from univariate analysis; R, random-effects model; F, fixed-effects model.