Table 1.
The associations of MMPs with overall survival (OS).
Fig 1.
MMP9 expression was correlated with glioma grade.
(A) MMP9 expression was correlated with glioma grade (p<0.001). Glioma of grade IV showed a significantly increased in MMP9 expression compared to grade II and III gliomas (p<0.0001, p<0.0001, respectively). MMP9 expression level in grade III gliomas was markedly higher than that in grade II gliomas (p<0.0001). (B, C) Likelihood ratio test showed that MMP9 was significantly associated with tumor grade in two independent glioma dataset (p<0.001, p<0.001, respectively) * p< 0.05; **** p<0.0001.
Table 2.
Clinical and molecular pathological features of primary GBM samples in association with MMP9 expression.
Fig 2.
Kaplan-Meier plots of progression-free and overall survival duration in patients with primary GBM.
(A, B) Kaplan–Meier survival analysis of PFS and OS duration in 78 primary GBM patients according to MMP9 mRNA expression. Patients with low MMP9 expression had a longer OS and PFS than patients with high MMP9 expression (p = 0.0012 and p = 0.0066, respectively). (C, D) Two independent datasets (REMBRANDT and GSE16011) were used to validate the association between MMP9 expression and survival. Patients with lower MMP9 expression also had improved OS in the two validation datasets (p = 0.0338 and p<0.0001, respectively).
Table 3.
Cox Hazard Regression Analysis of the Associations of Clinicopathologic Factors and MMP9 expression for Survival (n = 78).
Fig 3.
Kaplan-Meier estimates of progression-free and overall survival according to MMP9 expression and treatment groups.
(A, B) Kaplan–Meier survival analysis indicated that patients treated with RT combined with TMZ therapy (n = 28) had better OS and PFS (OS: p = 0.0002; PFS: p = 0.0002) than patients with RT alone (n = 11) in low MMP9 group (n = 39). (C, D) However, in the high MMP9 group (n = 39), there was no significant survival benefit of the combination treatment (RT alone: n = 17; RT combined TMZ: n = 22).
Fig 4.
Kaplan-Meier estimates of progression-free and overall survival according to MMP9 expression, MGMT methylation status and treatment groups.
(A, B, C, D) In the low MMP9 group, patients who received the combination therapy showed improved OS and PFS regardless of whether the MGMT promoter was methylated (n = 20; RT alone: n = 6; RT combined TMZ: n = 14) or unmethylated (n = 18; RT alone: n = 4; RT combined TMZ: n = 14). (E, F, G, H) In the high MMP9 group, TMZ chemotherapy resulted in better OS but not better PFS in patients with an unmethylated MGMT promoter (n = 29; RT alone: n = 12; RT combined TMZ: n = 17), while TMZ did not benefit patients with a methylated MGMT promoter (n = 9; RT alone: n = 4; RT combined TMZ: n = 5).