A Pyroptosis-Related Gene Signature Associated with Prognosis and Tumor Immune Microenvironment in Gliomas

Abstract

Background Pyroptosis is a novel form of cell death that plays a significant role in cancer, while the prognostic values of pyroptosis-related genes in gliomas have not been revealed. Methods We analyzed the RNA-seq and clinical data of gliomas from the University of California Santa Cruz (UCSC) Xena database to determine differentially expressed pyroptosis-related genes. Based on these genes, a pyroptosis genes signature was constructed after univariate Cox analysis and Lasso Cox analyses. The sensitivity and specificity of pyroptosis genes signature were verified by the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, we explored the association of risk signatures with tumor microenvironment and immune cell infiltration. Results Of 15 differentially expressed pyroptosis-related genes, three genes of BCL2 associated X (BAX), caspase 3 (CASP3), and caspase 4 (CASP4) were used to construct the risk signature. The effectiveness of risk signature for predicting survival at 1, 3, 5 years was performed by the receiver operating characteristic curve (ROC), and the area under curves (AUC) was 0.739, 0.817, and 0.800, respectively. Functional enrichment results showed signal transduction, cell adhesion, immune response, and inflammatory response were enriched. The immune analysis revealed that pyroptosis had a remarkable effect on the immune microenvironment. Conclusion In this study, we constructed a pyroptosis-related gene signature, which can serve as a potential biomarker for predicting the survival of glioma patients. Additionally, we suggested that pyroptosis may promote gliomas development by inducing chronic inflammation microenvironment.

Pyroptosis-related gene signature: A predictor for overall survival, immunotherapy response, and chemosensitivity in patients with pancreatic adenocarcinoma

“…Immune checkpoint inhibitors(ICIs) known as an important immunotherapy option have showed promising therapeutic effects in various solid tumors including melanoma, bladder as well as renal cancer [ 73 ].However, this novel therapeutic approach failed to elicit response in most of PAAD patients, and tumor genotyping system that identify patients more likely to benefit from ICIs treatment was limited. Our research revealed that patients in low-risk group exhibited higher expression of ICIs-related moleculars such as PD-1, CTLA-4, TIM-3 and CXCR4, and it has been reported that the expression level of ICIs-related moleculars can serve as a biomarker to forecast the efficacy of ICIs therapy [ 23 ]. PD-1 is expressed on a variety of immune cells especially on activated T cells, and also marked as an indicator for activation of CD8 + T-cell [ 74 ], which consistent with the finding that higher expression of PD-1 indicated better prognosis.…”

“…On the contrary, the proinflammatory cell death induced by pyroptosis could accelerate immune evasion and facilitate a suitable tumor microenvironment for tumor growth [ 20 ]. To date, the survival predicting ability of pyroptosis-related signature has been extensively studied in multiple tumor types including lung adenocarcinoma(LUAD) [ 21 ], hepatocellular cancer [ 22 ] and gliomas [ 23 ].Unfortunately, the clinical prognostic significance of pyroptosis in PAAD is still unclarified.…”

ROS induced pyroptosis in inflammatory disease and cancer

“…Additionally, periodontitis (a type of chronic inflammation) promotes breast cancer metastasis in the early stages through pyroptosis ( 123 ), Zunjie Zhou et al. discovered that pyroptosis may promote glioblastoma development by inducing chronic inflammatory microenvironments ( 124 ), indirectly proving the role of ROS-induced chronic inflammation in promoting tumors through pyroptosis.…”