Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis

Wang, Wenxin; Gao, Xin; Kang, Ning; Wang, Chen; Li, Chenyang; Yu, Huan; Zhang, Xiaolan

doi:10.1038/s41598-023-44853-6

Cited by 2 publications

(1 citation statement)

References 41 publications

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“…Accumulating evidence highlighting the robust association between MAFLD and IBD, the specific molecules and mechanisms underlying this association remain elusive 32 , 33 . Research revealed that decreasing levels of butyric acid could exacerbate damage to the intestinal barrier, affect the liver through leakage through the damaged intestinal barrier, leading to MAFLD 31 .…”

Section: Discussionmentioning

confidence: 99%

Exploring the butyrate metabolism-related shared genes in metabolic associated steatohepatitis and ulcerative colitis

Deng,

Liu,

Chen

et al. 2024

Sci Rep

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Metabolic-associated steatohepatitis (MASH) and ulcerative colitis (UC) exhibit a complex interconnection with immune dysfunction, dysbiosis of the gut microbiota, and activation of inflammatory pathways. This study aims to identify and validate critical butyrate metabolism-related shared genes between both UC and MASH. Clinical information and gene expression profiles were sourced from the Gene Expression Omnibus (GEO) database. Shared butyrate metabolism-related differentially expressed genes (sBM-DEGs) between UC and MASH were identified via various bioinformatics methods. Functional enrichment analysis was performed, and UC patients were categorized into subtypes using the consensus clustering algorithm based on sBM-DEGs. Key genes within sBM-DEGs were screened through Random Forest, Support Vector Machines-Recursive Feature Elimination, and Light Gradient Boosting. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) analysis on independent datasets. Additionally, the expression levels of characteristic genes were validated across multiple independent datasets and human specimens. Forty-nine shared DEGs between UC and MASH were identified, with enrichment analysis highlighting significant involvement in immune, inflammatory, and metabolic pathways. The intersection of butyrate metabolism-related genes with these DEGs produced 10 sBM-DEGs. These genes facilitated the identification of molecular subtypes of UC patients using an unsupervised clustering approach. ANXA5, CD44, and SLC16A1 were pinpointed as hub genes through machine learning algorithms and feature importance rankings. ROC analysis confirmed their diagnostic efficacy in UC and MASH across various datasets. Additionally, the expression levels of these three hub genes showed significant correlations with immune cells. These findings were validated across independent datasets and human specimens, corroborating the bioinformatics analysis results. Integrated bioinformatics identified three significant biomarkers, ANXA5, CD44, and SLC16A1, as DEGs linked to butyrate metabolism. These findings offer new insights into the role of butyrate metabolism in the pathogenesis of UC and MASH, suggesting its potential as a valuable diagnostic biomarker.

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Section: Discussionmentioning

confidence: 99%

Exploring the butyrate metabolism-related shared genes in metabolic associated steatohepatitis and ulcerative colitis

Deng,

Liu,

Chen

et al. 2024

Sci Rep

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Blood transcriptomics identifies FEZ1 as a novel non-invasive diagnostic biomarker for inflammatory bowel disease

Delkhah

2024

Preprint

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In comparison with conventional diagnostic methods, blood biomarkers are an easily accessible source for diagnosing inflammatory bowel disease (IBD). To identify such a biomarker, an integrated transcriptomics approach was employed to detect RNAs exhibiting diagnostic efficacy. For this purpose, four gene expression datasets obtained from blood specimens were integrated (GSE119600, GSE94648, GSE86434, and GSE71730). After determining differentially expressed genes in Crohn’s disease and ulcerative colitis, DEGs in IBD were defined as genes with a consistent direction of alteration in both disorders. Mapping the PPI network for these genes revealed TNF as the central hub gene. Subsequently, weighted gene-expression network analysis (WGCNA) was carried out to determine IBD-specific modules. Considering the degree metrics, module membership, and gene significance, PRF1 was the only gene discerned as a hub gene in a module that was prominently enriched in IBD. Genes with converging results from differential expression analysis and WGCNA were subjected to the random forest decision tree-based and LASSO regression methods. Following the identification of FEZ1 and NLRC5 as genes highlighted by both analyses, ROC analysis was applied to assess their diagnostic potential. Although both genes demonstrated acceptable diagnostic efficacy in the integrated data, only FEZ1 was considered as a potential biomarker based on the replication of results in validation datasets (GSE119600, GSE94648, GSE86434, and GSE71730). While autophagy is currently the most convincing explanation for the involvement of FEZ1 in IBD, further investigations are required to elucidate its immunological role.

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Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis

Cited by 2 publications

References 41 publications

Exploring the butyrate metabolism-related shared genes in metabolic associated steatohepatitis and ulcerative colitis

Exploring the butyrate metabolism-related shared genes in metabolic associated steatohepatitis and ulcerative colitis

Blood transcriptomics identifies FEZ1 as a novel non-invasive diagnostic biomarker for inflammatory bowel disease

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