Abstract
BackgroundTissue 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.ObjectiveThis study aimed to explore the role of TIMP expression and immune infiltration in GBM.MethodsOncomine, GEPIA, OSgbm, LinkedOmics, STRING, GeneMANIA, Enrichr, and TIMER were used to conduct differential expression, prognosis, and immune infiltration analyses of TIMPs in GBM.ResultsAll 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.ConclusionsOur study inspires new ideas for the role of TIMPs in GBM and provides new directions for multiple treatment modalities, including immunotherapy, in GBM.
Highlights
Glioblastoma (GBM) is the most aggressive of the four grades of gliomas classified by WHO [1] and accounts for 17% of all primary brain tumours [2]
High TIMP3 expression correlated with better overall survival (OS) and disease-specific survival (DSS) 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
Summary
Glioblastoma (GBM) is the most aggressive of the four grades of gliomas classified by WHO [1] and accounts for 17% of all primary brain tumours [2]. Matrix metalloproteinases (MMPs) are a family of zincdependent endopeptidases implicated in degrading components of the extracellular matrix (ECM) [4], tumour cell invasion and angiogenesis, and suppression of antitumour immune surveillance [5]. Several studies have indicated that MMPs are related to increased invasiveness [8] and a poor prognosis [9] in GBM. 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. The link between TIMPs and glioblastoma (GBM) is unclear
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