Comprehensive analysis of the role of Caspases in glioma.

Abstract

Caspases (CASPs) are attractive targets for cancer therapy. Many prognostic models based on gene signatures include genes from the CASPs family in diffuse glioma. CASP3, CASP4 and CASP6 in glioma have been studied individually. However, specialized comprehensive analysis of the roles CASPs family in glioma is lacking. Therefore, this study utilized bioinformatics methods to investigate this issue. CASP1-10 expressions were significantly up-regulated in LGG and GBM and glioma, and varied significantly across different clinical subgroups of glioma and LGG and various cell types, and most of CASP1-10 showed significant differences in recurrence status of LGG. 10 signatures (CASP1-10) were associated with poor overall survival (OS) in glioma and LGG and GBM. However, pan-cancer survival analysis showed that CASP1-10 were associated with the prognosis of LGG, but not GBM. CASP1-10 were related to poor prognosis of glioma and LGG, except for CASP9, which was the opposite of a protective factor. CASP1-10 were independent prognostic factors for OS in glioma and LGG, except for CASP5, and also for recurrence-free survival (RFS) in LGG. Most of CASP1-10 were also independent prognostic factors for disease-specific survival (DSS) and progression-free interval (PFI) and had diagnostic value in glioma and LGG. Genetic alterations of CASP1-10 genes set were associated with poor prognosis in LGG. CASP1-10 were involved in immune infiltration and programmed cell death in glioma and LGG and GBM, and might promote the apoptosis of immune cells. Compared to GBM, CASP1-10 had a more significant impact on the prognosis, cancer-related pathways, and immune infiltration in LGG, indicating that CASP1-10 might play important roles in the recurrence and progression of LGG, and might be promising therapeutic targets for LGG. Therefore, it is speculated that natural caspase inhibitor p35 may be a promising drug for the treatment of glioma, especially for LGG.