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Characterization of PANoptosis-related genes in Crohn's disease by integrated bioinformatics, machine learning and
Yang Yang1,2,3,4, Alphonse Houssou Hounye5, Yiqian Chen1,2,3
1Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
Currently, the biological understanding of Crohn's disease (CD) remains limited. PANoptosis is a revolutionary form of cell death reported to participate in numerous diseases, including CD. In our study, we aimed to uncover the roles of PANoptosis in CD. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified by overlapping PANoptosis-related genes and differentially expressed genes between CD and normal samples in a combined microarray dataset. Three machine learning algorithms were adopted to detect hub DE-PRGs. To stratify the heterogeneity within CD patients, nonnegative matrix factorization clustering was conducted. In terms of immune landscape analysis, the "ssGSEA" method was applied. qRT-PCR was performed to examine the expression levels of the hub DE-PRGs in CD patients and colitis model mice. Ten hub DE-PRGs with satisfactory diagnostic performance were identified and validated: CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1 and XBP1. These genes displayed significant associations with certain immune cell types and CD-related genes. We also constructed gene‒microRNA, gene‒transcription factor and drug‒gene interaction networks. CD samples were classified into two PANoptosis patterns according to the expression levels of the hub DE-PRGs. Our results suggest that PANoptosis plays a nonnegligible role in CD by modulating the immune system and interacting with CD-related genes.
Insights
PANoptosis, a novel cell death pathway, is implicated in Crohn's disease (CD). This study identified key PANoptosis-related genes that could help stratify CD patients and understand disease mechanisms.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- The biological mechanisms underlying Crohn's disease (CD) are not fully understood.
- PANoptosis, a recently identified cell death pathway, is increasingly recognized for its role in various diseases, including CD.
Purpose of the Study:
- To investigate the role of PANoptosis in the pathogenesis of Crohn's disease.
- To identify and validate key PANoptosis-related genes (PRGs) associated with CD.
- To explore the potential of these genes in stratifying CD patients and understanding immune dysregulation.
Main Methods:
- Integrated analysis of microarray data to identify differentially expressed PRGs (DE-PRGs) in CD.
- Application of machine learning algorithms to pinpoint hub DE-PRGs.
- Nonnegative matrix factorization for patient stratification and ssGSEA for immune landscape analysis.
- Validation of hub DE-PRG expression in CD patients and a colitis mouse model using qRT-PCR.
Main Results:
- Ten hub DE-PRGs (CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1, XBP1) were identified with significant diagnostic value.
- These genes showed associations with specific immune cell types and CD-related genes.
- CD patients were classified into two distinct PANoptosis patterns based on hub DE-PRG expression, revealing heterogeneity.
Conclusions:
- PANoptosis plays a significant role in Crohn's disease pathogenesis.
- The identified hub DE-PRGs serve as potential biomarkers for CD diagnosis and patient stratification.
- Modulation of the immune system and interaction with CD-related genes are key mechanisms through which PANoptosis influences CD.
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