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

Chen-Cheng Dong; Qiu-Huan Zhang; Yan Zhang; Yujie Zhang; Hanyi Ruan; Tianyu Qin; Jie-Hua Zhao; Guo Wu; Zhou Zhu; Jian-Rong Yang

doi:10.1016/j.compbiomed.2023.106622

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

Comput Biol Med. 2023 Mar:155:106622. doi: 10.1016/j.compbiomed.2023.106622. Epub 2023 Feb 2.

Authors

Chen-Cheng Dong¹, Qiu-Huan Zhang¹, Yan Zhang², Yujie Zhang², Hanyi Ruan², Tianyu Qin², Jie-Hua Zhao³, Guo Wu¹, Zhou Zhu⁴, Jian-Rong Yang⁵

Affiliations

¹ Department of Colorectal and Anal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, China.
² Department of Colorectal and Anal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, China.
³ Department of Breast and Thyroid Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, China.
⁴ Department of Colorectal and Anal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, China. Electronic address: zhuzhou_chn@163.com.
⁵ Department of Breast and Thyroid Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, China. Electronic address: yangjianrong66@126.com.

PMID: 36780800
DOI: 10.1016/j.compbiomed.2023.106622

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: IPAF inflammasomes; Immunotherapy; Pan-cancer; Single-cell transcriptome sequencing; Tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cysteine
Databases, Factual
Humans
Immunotherapy
Inflammasomes*
Neoplasms*

Substances

Inflammasomes
Cysteine