Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning
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 investiga...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/3033 |
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| author | Zhengjian Wang Jin Liu Yuting Wang Hui Guo Fan Li Yinan Cao Liang Zhao Hailong Chen |
| author_facet | Zhengjian Wang Jin Liu Yuting Wang Hui Guo Fan Li Yinan Cao Liang Zhao Hailong Chen |
| author_sort | Zhengjian Wang |
| collection | DOAJ |
| description | 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 (<i>LY96</i>, <i>BCL2</i>, <i>IFNGR1</i>) 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. |
| first_indexed | 2024-03-11T09:39:20Z |
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| id | doaj.art-d6c87cbbf03d41218e7bce0b641ba37a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:39:20Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d6c87cbbf03d41218e7bce0b641ba37a2023-11-16T17:06:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243303310.3390/ijms24033033Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine LearningZhengjian Wang0Jin Liu1Yuting Wang2Hui Guo3Fan Li4Yinan Cao5Liang Zhao6Hailong Chen7Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, ChinaImmunogenic 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 (<i>LY96</i>, <i>BCL2</i>, <i>IFNGR1</i>) 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.https://www.mdpi.com/1422-0067/24/3/3033severe acute pancreatitisimmunogenic cell deathWGCNALASSOmachine learningimmune cell infiltration |
| spellingShingle | Zhengjian Wang Jin Liu Yuting Wang Hui Guo Fan Li Yinan Cao Liang Zhao Hailong Chen Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning International Journal of Molecular Sciences severe acute pancreatitis immunogenic cell death WGCNA LASSO machine learning immune cell infiltration |
| title | Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning |
| title_full | Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning |
| title_fullStr | Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning |
| title_full_unstemmed | Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning |
| title_short | Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning |
| title_sort | identification of key biomarkers associated with immunogenic cell death and their regulatory mechanisms in severe acute pancreatitis based on wgcna and machine learning |
| topic | severe acute pancreatitis immunogenic cell death WGCNA LASSO machine learning immune cell infiltration |
| url | https://www.mdpi.com/1422-0067/24/3/3033 |
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