Pyroptosis-related prognosis model, immunocyte infiltration characterization, and competing endogenous RNA network of glioblastoma

Abstract

Background Glioblastoma (GBM) has a high incidence rate, invasive growth, and easy recurrence, and the current therapeutic effect is less than satisfying. Pyroptosis plays an important role in morbidity and progress of GBM. Meanwhile, the tumor microenvironment (TME) is involved in the progress and treatment tolerance of GBM. In the present study, we analyzed prognosis model, immunocyte infiltration characterization, and competing endogenous RNA (ceRNA) network of GBM on the basis of pyroptosis-related genes (PRGs). Methods The transcriptome and clinical data of 155 patients with GBM and 120 normal subjects were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Lasso (Least absolute shrinkage and selection operator) Cox expression analysis was used in predicting prognostic markers, and its predictive ability was tested using a nomogram. A prognostic risk score formula was constructed, and CIBERSORT, ssGSEA algorithm, Tumor IMmune Estimation Resource (TIMER), and TISIDB database were used in evaluating the immunocyte infiltration characterization and tumor immune response of differential risk samples. A ceRNA network was constructed with Starbase, mirtarbase, and lncbase, and the mechanism of this regulatory axis was explored using Gene Set Enrichment Analysis (GSEA). Results Five PRGs (CASP3, NLRP2, TP63, GZMB, and CASP9) were identified as the independent prognostic biomarkers of GBM. Prognostic risk score formula analysis showed that the low-risk group had obvious survival advantage compared with the high-risk group, and significant differences in immunocyte infiltration and immune related function score were found. In addition, a ceRNA network of messenger RNA (CASP3, TP63)–microRNA (hsa-miR-519c-5p)–long noncoding RNA (GABPB1-AS1) was established. GSEA analysis showed that the regulatory axis played a considerable role in the extracellular matrix (ECM) and immune inflammatory response. Conclusions Pyroptosis and TME-related independent prognostic markers were screened in this study, and a prognosis risk score formula was established for the first time according to the prognosis PRGs. TME immunocyte infiltration characterization and immune response were assessed using ssGSEA, CIBERSORT algorithm, TIMER, and TISIDB database. Besides a ceRNA network was built up. This study not only laid foundations for further exploring pyroptosis and TME in improving prognosis of GBM, but also provided a new idea for more effective guidance on clinical immunotherapy to patients and developing new immunotherapeutic drugs.

Comprehensive Analysis of Granzymes and Perforin Family Genes in Pan-Cancer

“…These findings not only support the results of this study, but further support ongoing research demonstrating GZMK's role in breast cancer progression. Similarly, GZMB mutations in GBM and PRF1 mutations in colorectal cancer and UCEC align with literature suggesting the impact of these genes on patient survival in specific cancer types [56][57][58][59][60].…”

Development of a prognostic model for glioblastoma multiforme based on the expression levels of efferocytosis-related genes

“…The role of GZMB in apoptosis makes it an attractive anticancer target [ 31 ]. C9orf64 and GZMB were identified as the prognostic biomarkers for GBM by bioinformatics analysis [ 32 , 33 ]. In the present study, the expression levels of above-mentioned genes were significantly elevated and associated with GBM patients’ survival.…”

Identification of a novel gene signature with DDR and EMT difunctionalities for predicting prognosis, immune activity, and drug response in breast cancer

“…Therefore, we developed a gene signature based on dual-function to predict prognosis. And the prognostic role of the 6 genes we screened has been put forward in other cancer studies [23][24][25][26][27][28]. Furthermore, this is the rst study to explore novel prognostic markers for breast cancer using genes with dual functions of DDR and EMT, aiming to propose a new strategic direction for the treatment and prognostic evaluation of BRCA patients.…”