Significance of the association between hypoxia and pyroptosis-related genes in the prognostic prediction of glioblastoma: insights from model construction and validation.

Background: Tumor hypoxic environment can regulate pyroptosis and immune escape by affecting multiple signaling pathways, and synergistic targeting this interaction may be a promising strategy for tumor treatment. However, their connection in glioblastoma (GBM) remains unclear. This study aimed to construct hypoxia- and pyroptosis-related signatures for exploring their values in predicting prognosis of GBM. Methods: GBM expression profiles, hypoxia genes, and pyroptosis genes were collected from the following public databases: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genecards, and gene set enrichment analysis (GSEA). After obtaining the hypoxia- and pyroptosis-related differentially expressed genes (DEGs) within GBM Results: A total of 13 hypoxia- and 13 pyroptosis-associated genes were included in the risk models, respectively. Two models had high accuracy and stability in predicting GBM prognosis. Low-risk and high-risk groups identified by the model had different immune cell infiltration patterns. In the high-risk group, the abundance level of naïve B cells, plasma cells, and native CD4 T cells was inhibited, while levels of neutrophils were increased. In addition, the risk models could predict chemotherapy sensitivity. Of interest, pyroptosis-related genes showed a significant negative correlation with most hypoxia-related genes. Conclusions: These constructed prognostic models can effectively identify high-risk patients, and drugs targeting the hypoxia-pyroptosis axis have a broad application prospect in GBM.