Identification of a novel pyroptosis-related gene signature correlated with the prognosis of diffuse glioma patients

Yize Zhang; Feiyang Xi; Qing Yu; Weiming Lou; Ziqiang Zeng; Ning Su; Jianying Gao; Sainan Duan; Ying Deng; Sixuan Guo; Shuhui Lai; Xiaoli Tang; Jicai Zhang

doi:10.21037/atm-21-6011

Identification of a novel pyroptosis-related gene signature correlated with the prognosis of diffuse glioma patients

Ann Transl Med. 2021 Dec;9(24):1766. doi: 10.21037/atm-21-6011.

Authors

Yize Zhang^#¹, Feiyang Xi^#², Qing Yu^{3

4}, Weiming Lou⁵, Ziqiang Zeng^{6

7}, Ning Su^{6

7}, Jianying Gao⁸, Sainan Duan⁸, Ying Deng¹, Sixuan Guo¹, Shuhui Lai⁸, Xiaoli Tang^#⁹, Jicai Zhang^#¹⁰

Affiliations

¹ The Second Affiliated Hospital of Nanchang University, Nanchang, China.
² Queen Mary School of Nanchang University, Nanchang, China.
³ Department of Stomatology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
⁴ The Institute of Periodontal Disease, Nanchang University, Nanchang, China.
⁵ The Institute of Translational Medicine, Nanchang University, Nanchang, China.
⁶ The School of Public Health, Nanchang University, Nanchang, China.
⁷ Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang, China.
⁸ The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.
⁹ College of Basic Medical Science, Nanchang University, Nanchang, China.
¹⁰ Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

^# Contributed equally.

Abstract

Background: Diffuse glioma is the most common primary tumor of the central nervous system and has a poor prognosis. Recently, a new type of programmed cell death (PCD), pyroptosis, has been found to be widely involved in the process of tumor diseases. However, the expression of pyroptosis-related genes (PRGs) in diffuse gliomas and their relationship with prognosis have rarely been evaluated.

Methods: In this study, we obtained RNA sequencing and clinical data from the Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) of diffuse glioma patients. Simultaneously, differentially expressed PRGs between TCGA-Glioma tumor samples and the normal brain samples from the Genome Tissue Expression (GTEx) were investigated. Besides, univariate and multivariate Cox regression analysis were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve and principal component analysis (PCA) was undertaken to assess the prognostic capacity of the signature. Gene set enrichment analyses (GSEA) and single sample GSEA (ssGSEA) were used to further understand the molecular mechanisms and the difference of immune microenvironment. External validation of two separate cohorts from the CGGA database was then performed.

Results: Caspase 3 (CASP3) and interleukin-18 (IL18) were identified as potential prognostic biomarkers. A novel prognostic model was constructed to predict diffuse glioma patients' overall survival (OS) time. Patients in high-risk subgroup had shorter survival than those with high-risk with P<0.0001. GSEA and ssGSEA showed the activation of immune-related pathways and the extensive infiltration of immune cells [such as cytotoxic T cells, dendritic cells (DC), natural killer T cell (NKT), induced regulatory T cells (iTreg), naturally occurring regulatory T cells (nTreg)] in high-risk subgroup.

Conclusions: A novel two-PRGs prognostic signature based on gene expression was identified, which could predict diffuse glioma patients' OS time. Pyroptosis may be involved in the establishment of immune microenvironment in diffuse glioma.

Keywords: Caspase 3 (CASP3); Diffuse glioma; interleukin-18 (IL18); pyroptosis; risk signature.