Department of Colorectal and Anal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, China.
Department of Colorectal and Anal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, China.
Comput Biol Med. 2023 Mar;155:106622. doi: 10.1016/j.compbiomed.2023.106622. Epub 2023 Feb 2.
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.
IPA F（ICE 蛋白酶激活因子）是一种核苷酸结合/富含亮氨酸重复（NLR）蛋白，被称为半胱氨酸相关募集域 12（CARD12）。之前的研究仅讨论了 IPAF 炎性小体在特定肿瘤中的作用。IPA F 炎性小体在泛癌症中的作用尚不清楚。因此，我们对 33 种肿瘤中的 IPAF 炎性小体进行了全面分析。
我们使用了数据库，如癌症基因组图谱（TCGA）和基因型组织表达（GTEx），从 UCSC XENA（http://xena.ucsc.edu/）中检索和分析基因表达。使用单因素 Cox 回归分析和 Kaplan-Meier 生存分析来分析 IPAF 炎性小体对肿瘤患者预后的影响。此外，我们进行了以下分析：单样本基因集富集分析、单细胞水平功能状态分析、单细胞测序、免疫细胞浸润分析和肿瘤免疫功能障碍和排除（TIDE）评分。
首先，分析了 33 种肿瘤中 IPAF 炎性小体相关基因（IPAF-RGs）的差异表达。结果表明，IPA F-RGs 在八种肿瘤中存在显著差异表达。IPA F 炎性小体评分的预后意义在不同的肿瘤中是不同的。在大多数肿瘤中，IPA F 炎性小体评分与 CD8+T 细胞之间存在正相关。进一步分析表明，IPA F 炎性小体可能主要通过表达趋化因子如 CXCL9、CXCL10 和 CCL5 来调节效应 T 细胞的募集，从而影响肿瘤免疫。TIDE 和 IPA F 炎性小体评分的分析表明，在 11 种肿瘤中，IPA F 炎性小体与 TIDE 评分之间存在显著的负相关。
对各种肿瘤中的 IPAF 炎性小体进行了泛癌症分析。结果强调了 IPAF 炎性小体在预测患者免疫治疗反应中的潜在价值，并为未来的免疫治疗提供了新的方向。
