Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease

Abstract PANoptosis is one of several modes of programmed cell death (PCD) and plays an important role in many inflammatory and immune diseases. The role of PANoptosis in inflammatory bowel disease (IBD) is currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identifie...

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Main Authors: Minglin Zhang, Tong Liu, Lijun Luo, Yuxin Xie, Fen Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84911-1
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author Minglin Zhang
Tong Liu
Lijun Luo
Yuxin Xie
Fen Wang
author_facet Minglin Zhang
Tong Liu
Lijun Luo
Yuxin Xie
Fen Wang
author_sort Minglin Zhang
collection DOAJ
description Abstract PANoptosis is one of several modes of programmed cell death (PCD) and plays an important role in many inflammatory and immune diseases. The role of PANoptosis in inflammatory bowel disease (IBD) is currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, and pathway enrichment analyses were performed. LASSO regression model construction, a nomogram model, calibration curves, ROC and DCA curves were used to evaluate the predictive value of the model. Predicts transcription factors (TFs) and small-molecule drugs of DE-PRGs were analysed. Model genes and immuno-infiltration were analysed. The PANoptosis features of IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB and BAX. The enrichment analysis suggested that these genes were related to TNF signalling, NF-κB, pyroptosis and necroptosis. Machine learning identified three model genes: OGT, GZMB and CASP5. The nomogram model, calibration curves, ROC and DCA curves have strong predictive value. Immuno-infiltration analysis revealed that immune cell infiltration was increased in patients with IBD, and the model genes were closely related to the infiltration of various immune cells. The TFs associated with DE-PRGs were RELA, NFKB1, HIF1A, TP53 and SP1. In addition, the Connectivity Map (CMap) database identified the top 10 small-molecule compounds, including buspirone, chloroquine, spectinomycin and chlortetracycline. This study indicate that DE-PRGs model genes have good predictive ability for IBD. Moreover, PANoptosis may mediate the process of IBD through TNF signalling, NF-κB, pyroptosis, necroptosis and immune mechanisms. These results present a new horizon for the research and treatment of IBD.
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spelling doaj-art-02b336af7d50498cadc621218febae272025-01-19T12:17:22ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-84911-1Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel diseaseMinglin Zhang0Tong Liu1Lijun Luo2Yuxin Xie3Fen Wang4Department of Gastroenterology, The Third Xiangya Hospital, Central South UniversityDepartment of General Surgery, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese MedicineSchool of Medical Laboratory Science, Hebei North UniversityDepartment of Infectious Diseases, Affiliated Hospital of Zunyi Medical UniversityDepartment of Gastroenterology, The Third Xiangya Hospital, Central South UniversityAbstract PANoptosis is one of several modes of programmed cell death (PCD) and plays an important role in many inflammatory and immune diseases. The role of PANoptosis in inflammatory bowel disease (IBD) is currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, and pathway enrichment analyses were performed. LASSO regression model construction, a nomogram model, calibration curves, ROC and DCA curves were used to evaluate the predictive value of the model. Predicts transcription factors (TFs) and small-molecule drugs of DE-PRGs were analysed. Model genes and immuno-infiltration were analysed. The PANoptosis features of IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB and BAX. The enrichment analysis suggested that these genes were related to TNF signalling, NF-κB, pyroptosis and necroptosis. Machine learning identified three model genes: OGT, GZMB and CASP5. The nomogram model, calibration curves, ROC and DCA curves have strong predictive value. Immuno-infiltration analysis revealed that immune cell infiltration was increased in patients with IBD, and the model genes were closely related to the infiltration of various immune cells. The TFs associated with DE-PRGs were RELA, NFKB1, HIF1A, TP53 and SP1. In addition, the Connectivity Map (CMap) database identified the top 10 small-molecule compounds, including buspirone, chloroquine, spectinomycin and chlortetracycline. This study indicate that DE-PRGs model genes have good predictive ability for IBD. Moreover, PANoptosis may mediate the process of IBD through TNF signalling, NF-κB, pyroptosis, necroptosis and immune mechanisms. These results present a new horizon for the research and treatment of IBD.https://doi.org/10.1038/s41598-024-84911-1Bioinformatics analysisInflammatory bowel diseasePANoptosisDiagnostic biomarkersMolecular mechanism
spellingShingle Minglin Zhang
Tong Liu
Lijun Luo
Yuxin Xie
Fen Wang
Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
Scientific Reports
Bioinformatics analysis
Inflammatory bowel disease
PANoptosis
Diagnostic biomarkers
Molecular mechanism
title Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
title_full Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
title_fullStr Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
title_full_unstemmed Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
title_short Biological characteristics, immune infiltration and drug prediction of PANoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
title_sort biological characteristics immune infiltration and drug prediction of panoptosis related genes and possible regulatory mechanisms in inflammatory bowel disease
topic Bioinformatics analysis
Inflammatory bowel disease
PANoptosis
Diagnostic biomarkers
Molecular mechanism
url https://doi.org/10.1038/s41598-024-84911-1
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