Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning

Autor:	Zhengjian Wang, Jin Liu, Yuting Wang, Hui Guo, Fan Li, Yinan Cao, Liang Zhao, Hailong Chen
Rok vydání:	2023
Předmět:	WGCNA immune cell infiltration short-chain fatty acids Organic Chemistry LASSO General Medicine Catalysis Computer Science Applications Inorganic Chemistry machine learning immunogenic cell death Physical and Theoretical Chemistry Molecular Biology Spectroscopy severe acute pancreatitis
Zdroj:	International Journal of Molecular Sciences Volume 24 Issue 3 Pages: 3033
ISSN:	1422-0067
DOI:	10.3390/ijms24033033
Popis:	Immunogenic cell death (ICD) is a form of programmed cell death with a strong sense of inflammatory detection, whose powerful situational awareness can cause the reactivation of aberrant immunity. However, the role of ICD in the pathogenesis of severe acute pancreatitis (SAP) has yet to be investigated. This study aims to explore the pivotal genes associated with ICD in SAP and how they relate to immune infiltration and short-chain fatty acids (SCFAs), in order to provide a theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from the Gene Expression Omnibus (GEO). The use of differentially expressed gene (DEG) analysis; weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis allowed us to identify a total of three ICD-related hub genes (LY96, BCL2, IFNGR1) in SAP. Furthermore, single sample gene set enrichment analysis (ssGSEA) demonstrated that hub genes are closely associated with the infiltration of specific immune cells, the activation of immune pathways and the metabolism of SCFAs (especially butyrate). These findings were validated through the analysis of gene expression patterns in both clinical patients and rat animal models of SAP. In conclusion, the first concept of ICD in the pathogenesis of SAP was proposed in our study. This has important implications for future investigations into the pro-inflammatory immune mechanisms mediated by damage-associated molecular patterns (DAMPs) in the late stages of SAP.
Databáze:	OpenAIRE
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