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

作者：Muhammad Khan, Mei-Ling Ai, Kunpeng Du, Jingjing Song, Baiyao Wang, Jie Lin, Anbang Ren, Chengcong Chen, Zhong Huang, Wen‐Ze Qiu, Jiangyu Zhang, Yunhong Tian, Yawei Yuan · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.1062225 · 被引用次数：68 · 研究领域：Inflammasome and immune disorders、Ferroptosis and cancer prognosis、Inflammatory Biomarkers in Disease Prognosis

Background and aim: 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 anti-cancer immune responses. Methods: Utilizing the data available in The Cancer Genome Atlas (TCGA), pyroptosis-related genes' (PRGs) expression, genomic aberrations, and clinical significance were systematically analyzed in pan-cancer. A GSVA score was obtained to rate pyroptosis level and divide the cancers into pyroptosis-low and pyroptosis-high groups. Immunohistochemistry (IHC) was used to evaluate the differential expression of major PRGs (GSDMC, GSDMD, GSDME, NLRP3, NLRC4, IL1B) in selected tumor types (COAD, HNSC, KIRC, LIHC, LUAD, LUSC). Selection of tumors for immunohistochemistry (IHC) was based on their expression pattern in TCGA cancers, clinical relevance, tumor epidemiology, and sample availability. Results: Differential expression of PRGs was evident in various cancers and associated with prognosis which was driven by genomic variations and epigenetic abnormalities, such as single nucleotide variations (SNVs), copy number variation (CNV) and DNA methylation level. For example, methylation of PRGs in lower grade glioma (LGG), uveal melanoma (UVM) and kidney renal clear cell carcinoma (KIRC) were predictive of improved survival as upregulation of PRGs was risky in these cancers. Pyroptosis level significantly differentiated tumor from normal s...