Prognostic characterization of the pyroptosis-related subtypes and tumor microenvironment infiltration in glioma.

Abstract

Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient. The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P< 0.001; validation cohort, P< 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score. Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies.