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Previous studies majorly focused on the role of driver gene variation in the occurrence, development and treatment of glioma. Here, we revealed the effect of signaling pathway abnormality by accumulated genetic mutations on patient survival and explored potential mechanism in glioma. We found that abnormalities of three signaling pathways, including autophagy-animal, focal adhesion and neuroactive ligand-receptor interaction, were associated with progression-free survival (PFS) in glioma. Based on the three pathways, we constructed and validated a biological pathway score (BPS) model to predict patient prognosis. Both PFS and overall survival (OS) were poorer in glioma patients with high BPS. In the glioma patients with high BPS, mutation frequencies of PTEN, TTN and EGFR were significantly increased. Immune checkpoints (PD-1, PD-L1 and TIM-3) were strikingly expressed in the high BPS patients with glioma, despite observed high levels of infiltrating immune cells. Differential expression genes in the high BPS patients were enriched in proliferation-related pathways. These results revealed potential reasons of poor prognosis in the high BPS patients with glioma. In addition, we found that low BPS patients with glioma might benefit from sevoflurane during surgery anesthesia. Overall, this study exhibited that the abnormalities of PFS-related signaling pathways by genetic mutations impacted survival of patients and revealed potential mechanism of poor PFS in glioma.