Comprehensive landscape of the IPAF inflammasomes in pan-cancer: A bulk omics research and single-cell sequencing validation

炎症体 医学 内科学 炎症
作者
Chen‐Cheng Dong,Qiu-huan Zhang,Yan Zhang,Yujie Zhang,Hanyi Ruan,Tianyu Qin,Jie-hua Zhao,Guan‐Ling Wu,Zhen Zhu,Jianrong Yang
出处
期刊:Computers in Biology and Medicine [Elsevier]
卷期号:155: 106622-106622
标识
DOI:10.1016/j.compbiomed.2023.106622
摘要

IPAF (ICE-protease Activating Factor) is a nucleotide-binding/leucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (http://xena.ucsc.edu/) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis: Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8+ T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.
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