Background Tissue inhibitors of metalloproteinase (TIMP) family proteins are peptidases involved in extracellular matrix (ECM) degradation. Various diseases are related to TIMPs, and the primary reason is that TIMPs can indirectly regulate remodelling of the ECM and cell signalling by regulating matrix metalloproteinase (MMP) activity. However, the link between TIMPs and glioblastoma (GBM) is unclear. Objective This study aimed to explore the role of TIMP expression and immune infiltration in GBM. Methods Oncomine, GEPIA, OSgbm, LinkedOmics, STRING, GeneMANIA, Enrichr, and TIMER were used to conduct differential expression, prognosis, and immune infiltration analyses of TIMPs in GBM. Results All members of the TIMP family had significantly higher expression levels in GBM. High TIMP3 expression correlated with better overall survival (OS) and disease-specific survival (DSS) in GBM patients. TIMP4 was associated with a long OS in GBM patients. We found a positive relationship between TIMP3 and TIMP4, identifying gene sets with similar or opposite expression directions to those in GBM patients. TIMPs and associated genes are mainly associated with extracellular matrix organization and involve proteoglycan pathways in cancer. The expression levels of TIMPs in GBM correlate with the infiltration of various immune cells, including CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells. Conclusions Our study inspires new ideas for the role of TIMPs in GBM and provides new directions for multiple treatment modalities, including immunotherapy, in GBM.
Low-grade glioma (LGG) is one of the most common brain tumors and often develops into the worst glioblastoma (GBM). Pyroptosis is related to inflammation and immunization. It has been demonstrated to influence the progression of a variety of cancers. However, the value of pyrosis-related genes (PRGs) in LGG remains unclear. Public TCGA-LGG data are used to analyze the differential expression and genetic variation of PRGs in LGG. Subsequently, this paper identifies pyroptosis-related subtypes and constructs prognostic models. This paper analyzes the expression and function of selected CASP5 in LGG and constructs a ceRNA regulatory network. Final CASP5-related immune infiltration analysis and methylation analysis are performed. Most PRGs are differentially expressed and altered in LGG. Subtypes and prognostic models based on PRGs not only have good functions but also have a great connection with immune infiltration. Enrichment analysis of PRGs with prognostic value of LGG also shows functions correlated mainly with immunity and inflammation. CASP5 is significantly differentially expressed in different grades of gliomas and different prognoses. Despite fewer mutations, CASP5 has a clear correlation for both immune cells and immune checkpoint molecules in the LGG microenvironment. Its methylation may also have a role in the prognosis of LGG. This paper shows the association of pyrosis-related subtypes, prognostic models, and genes, with immune infiltration.
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