Pyroptosis relates to tumor microenvironment remodeling and prognosis: A pan-cancer perspective

• DOI: 10.3389/fimmu.2022.1062225
• Publication Date: 2022-12-20T08:28:36Z
• Authors: Muhammad Khan; Meiling Ai; Kunpeng Du; Jingjing Song; Baiyao Wang; Jie Lin; Anbang Ren; Chengcong Chen; Zhong Huang; Wenze Qiu; Jiangyu Zhang; Yunhong Tian; Yawei Yuan
• Keywords: Pyroptosis

Pyroptosis is an inflammatory form of programmed cell death implicated in inflammation and disease. Moreover, inducing pyroptosis has been appreciated as anti-cancer therapy for its ability to unleash immune responses.Utilizing the data available The Cancer Genome Atlas (TCGA), pyroptosis-related genes' (PRGs) expression, genomic aberrations, clinical significance were systematically analyzed pan-cancer. A GSVA score was obtained rate level divide cancers into pyroptosis-low pyroptosis-high groups. Immunohistochemistry (IHC) used evaluate differential expression major PRGs (GSDMC, GSDMD, GSDME, NLRP3, NLRC4, IL1B) selected tumor types (COAD, HNSC, KIRC, LIHC, LUAD, LUSC). Selection tumors immunohistochemistry based on their pattern TCGA cancers, relevance, epidemiology, sample availability.Differential evident various associated with prognosis which driven by variations epigenetic abnormalities, such single nucleotide (SNVs), copy number variation (CNV) DNA methylation level. For example, lower grade glioma (LGG), uveal melanoma (UVM) kidney renal clear carcinoma (KIRC) predictive improved survival upregulation risky these cancers. significantly differentiated from normal samples 15 exhibited a progressive trend cancer stage, observed among subtypes, showed significant association prognosis. Higher worst majority terms OS (KIRC, LGG, UVM), PFS (GBM, PRAD, THCA, THYM) DSS (KIRC LGG) estimated Kaplan-Meier curves. strongly indicative hot microenvironment high presence CD8+ T other subtypes. Several oncogenic pathways, P53 pathway, repair, KRAS signaling, epithelial-mesenchymal transition (EMT), IL6 JAK STAT3 IL2 STAT5 PI3K AKT MTOR signaling angiogenesis, enriched pyroptosis-hi subgroups across cancers.Genetic alterations greatly influence relatively irrespective Overall, our study reveals critical role highlights pyroptosis-based therapeutic vulnerabilities.