Comprehensive Characterization of Pyroptosis Patterns with Implications in Prognosis and Immunotherapy in Low-Grade Gliomas.

Zijian Zhou,Luo Li,Wenbo Jiang,Jinhong Wei,Bin Lu,Yue Bao,Weimin Wang

doi:10.3389/fgene.2021.763807

Zijian Zhou, Luo Li + Show 5 more

Open Access

https://doi.org/10.3389/fgene.2021.763807

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Abstract

Background: Due to high heterogeneity and mortality of low-grade gliomas (LGGs), it is of great significance to find biomarkers for prognosis and immunotherapy. Pyroptosis is emerging as an attractive target in cancer research for its effect on tumor immune microenvironment (TIME). However, the investigation of pyroptosis in LGGs is insufficient. Methods: LGG samples from TCGA and CGGA database were classified into two pyroptosis patterns based on the expression profiles of 52 PRGs using consensus clustering. A prognostic model was constructed by using the LASSO-COX method. ESTIMATE algorithm and single sample gene set enrichment analysis (ssGSEA) were used to characterize the TIME. Based on the differentially expressed genes between two pyroptosis patterns, favorable and unfavorable pyroptosis gene signatures were determined. Pyroptosis score scheme was constructed to quantify the pyroptosis patterns through gene set variation analysis (GSVA) method. Two external datasets and immunotherapy cohort from CGGA and GEO database were used to validate the predictive value of the pyroptosis score. The Human Protein Atlas website and Western blotting were utilized to confirm the expression of the selected genes in the prognostic model in LGGs. Results: Distinct overall survival and immune checkpoint blockage therapeutic responses were identified between two pyroptosis patterns. A low pyroptosis score in LGG patients implies higher overall survival, poor immune cell infiltration, and better response to immunotherapy of immune checkpoint blockage. Conclusion: Our findings provided a foundation for future research targeting pyroptosis and opened a new sight to explore the prognosis and immunotherapy from the angle of pyroptosis in LGGs.

Highlights

Low-grade gliomas (LGGs) represent a group of common malignant tumors in the central nervous system especially for younger patients, mainly composed of grade II-III gliomas including astrocytoma, oligoastrocytoma, and oligodendroglioma according to the World Health
Our findings provided a foundation for future research targeting pyroptosis and opened a new sight to explore the prognosis and immunotherapy from the angle of pyroptosis in LGGs
The RNA sequencing (RNA-seq) data consisting of 508 LGGs samples and the corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA, http:// cancergenome.nih.gov/) database

Summary

Introduction

Organization classification system, and differ with high-grade glioma (glioblastoma, GBM) in biological and clinicopathological characteristics (Cancer Genome Atlas Research et al, 2015; Hoshide and Jandial, 2016; Ostrom et al, 2018; Sidaway, 2020). Due to the high heterogeneity of LGGs, the traditional classification is not satisfactory for predicting the prognosis even for patients with the same diagnosis. As a novel therapeutic strategy, immunotherapy has been extensively investigated in more and more cancers and durable responses to immune checkpoint blockage (ICB) treatment in many other forms of cancers have drawn increasing attention in gliomas (McGranahan et al, 2019). Due to high heterogeneity and mortality of low-grade gliomas (LGGs), it is of great significance to find biomarkers for prognosis and immunotherapy. Pyroptosis is emerging as an attractive target in cancer research for its effect on tumor immune microenvironment (TIME).

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Results

Conclusion