Article Figures & Data
Figures
- Figure 1
The workflow and sample selection criteria of this study.
- Figure 2
The effect of IDH mutation on MGMT promoter methylation in GBM. (A) Heatmap showing the methylation levels of CpG sites 75–78 in the MGMT promoter in GBM samples with different IDH mutant status. For the MGMT promoter, the average methylation level of CpG sites 75–78 is denoted unmethy (unmethylated), <10%; weak methy (methylated), ≥10% and <30%; or methy, ≥30%. (B) The distribution of average methylation levels of CpG sites 75–78 was compared between IDH-wildtype and IDH-mutant GBM. ****P < 0.0001 calculated by the chi-square test. (C) The age of IDH-wildtype and IDH-mutant patients with GBM was compared. ****P < 0.0001 calculated by the nonparametric test. (D) The gender distribution was compared between IDH-wildtype and IDH-mutant patients with GBM.
- Figure 3
Survival analysis of IDH-mutant GBM with different MGMT promoter methylation levels. (A, B) Kaplan-Meier curves for PFS and OS of IDH-mutant patients with GBM in different methylation groups. (C, D) Kaplan-Meier curves for PFS and OS of IDH-mutant patients with GBM stratified by different cutoff values. (E, F) Kaplan-Meier curves for PFS and OS of IDH-wildtype patients with GBM in different methylation groups. (G, H) Kaplan-Meier curves for PFS and OS of IDH-wildtype patients with GBM stratified by different cutoff values. P-value calculated by the log-rank test. MGMT promoter methylation levels were calculated on the basis of the average methylation levels of CpG sites 75–78.
- Figure 4
Validation of the predictive value of MGMT promoter methylation in another cohort of TMZ treated IDH-mutant GBM. (A) Kaplan-Meier curves for PFS of IDH-mutant patients with GBM in different methylation groups. (B) Kaplan-Meier curves for PFS of IDH-mutant patients with GBM, stratified by different cutoff values. (C) Kaplan-Meier curves for OS of IDH-mutant patients with GBM in different methylation groups. (D) Kaplan-Meier curves for OS of IDH-mutant patients with GBM, stratified by different cutoff values. P-value calculated by the log-rank test. MGMT promoter methylation levels were calculated on the basis of the average methylation levels of CpG sites 76–79.
Tables
Cohort A (CpGs 75–78, n = 50) Cohort B (CpGs 76–79, n = 25) P Median age (range) 41 (26–63) 43 (29–66) 0.3887a Gender 1.0000b Male 30 60.0% 15 60.0% Female 20 40.0% 10 40.0% Type 0.4091b Primary 23 46.0% 9 36.0% Recurrent/secondary 27 54.0% 16 64.0% Resection 0.0228b Gross total 33 66.0% 8 32.0% Subtotal 16 32.0% 13 52.0% Unknown 1 2.0% 4 16.0% Median KPS (range) 70 (50–90) 70 (50–90) 0.5464b <70 17 34.0% 9 36.0% ≥70 22 44.0% 16 64.0% Unknown 11 22.0% 0 0.0% TMZ cycles 0.8511b ≥3 and <6 13 26.0% 6 24.0% ≥6 37 74.0% 19 76.0% MGMT promoter methylation 0.5431b ≥30% 14 28.0% 11 44.0% ≥20%, <30% 8 16.0% 4 16.0% ≥10%, <20% 16 32.0% 6 24.0% <10% 12 24.0% 4 16.0% Median PFS (months) 10.57 8.32 0.5711c Median OS 16.13 13.2 0.3240c aCalculated by the nonparametric test; bCalculated by the chi-square test; cCalculated by the log-rank test in Kaplan-Meier curves.
- Table 2
Comparison of characteristics of IDH-mutant GBM samples with or without MGMT methylation (cutoff ≥30%) in cohort A
Unmethylated (n = 35) Methylated (n = 15) P Median age (range) 41 (26–63) 39 (33–62) 0.4529a Gender 0.2077b Male 23 65.7% 7 46.7% Female 12 34.3% 8 53.3% Type 0.1935b Primary 14 40.0% 9 60.0% Recurrent 21 60.0% 6 40.0% Resection 0.1053b Gross total 26 74.3% 8 53.3% Subtotal 8 22.9% 7 46.7% Unknown 1 2.9% 0 0.0% TMZ cycles 0.9706b ≥3 and <6 9 25.7% 4 26.7% ≥6 30 85.7% 13 86.7% KPS 0.6479b <70 12 34.3% 5 33.3% ≥70 14 40.0% 8 53.3% Unknown 9 25.7% 2 13.3% Median PFS (months) 9.33 26.04 0.0012c Median OS (months) 13.1 35.8 0.0004c aCalculated by the nonparametric test; bCalculated by the chi-square test; cCalculated by the log-rank test in Kaplan-Meier curves.
Univariate Cox analysis Multivariate Cox analysis P HR 95% CI for HR P HR 95% CI for HR Lower Higher Lower Higher Age 0.761 0.995 0.963 1.028 – – – – Gender (female vs. male) 0.223 0.663 0.343 1.283 – – – – MGMT (unmethy vs. methy) 0.001 3.691 1.689 8.063 0.002 3.560 1.600 7.920 Extent of resection (total vs. subtotal) 0.470 1.287 0.649 2.549 – – – – Type (primary vs. recurrent/secondary) 0.005 0.366 0.182 0.733 0.010 0.384 0.186 0.794 HR, hazard ratio; CI, confidence interval; methy, methylated; unmethy, unmethylated.
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