Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration

Li, Ting; Liu, Weidong; Hui, Wenjia; Shi, Tian; Liu, Huan; Feng, Yan; Gao, Feng

doi:10.1155/2022/4983471

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…However, interdisciplinary studies on comorbidities are relatively rare, and the prognosis for patients is poor. Both ankylosing spondylitis and inflammatory bowel disease are systemic, progressive, and recurrent chronic diseases [ 39 , 40 ]. According to epidemiology, the incidence of both diseases is increasing.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of “Treating Different Diseases with the Same Treatment” by Qiangji Jianpi Decoction in Ankylosing Spondylitis Combined with Inflammatory Bowel Disease: A Comprehensive Analysis of Multiple Methods

Zhang,

Zhou,

Qian

2024

Gastroenterology Research and Practice

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Background. Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are prevalent autoimmune disorders that often co-occur, posing significant treatment challenges. This investigation adopts a multidisciplinary strategy, integrating bioinformatics, network pharmacology, molecular docking, and Mendelian randomization, to elucidate the relationship between AS and IBD and to investigate the potential mechanisms of traditional Chinese medicine formulations, represented by Qiangji Jianpi (QJJP) decoction, in treating these comorbid conditions. Methods. We utilized databases to pinpoint common targets among AS, IBD, and QJJP decoction’s active compounds through intersection analysis. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we mapped a network in Cytoscape, isolating critical targets. Molecular docking with AutoDock validated the affinity between targets and compounds. ROC analysis and dataset validation assessed diagnostic performance, while Gene Set Enrichment Analysis (GSEA) offered pathway insights. Mendelian randomization explored the AS-IBD causal relationship. Results. Screening identified 105 targets for QJJP decoction, 414 for AS, and 2420 for IBD, with 85 overlapping. These targets predominantly participate in organismal responses and DNA transcription factor binding, with a significant cellular presence in the endoplasmic reticulum and vesicle lumen. Molecular docking, facilitated by Cytoscape, confirmed IL1A, IFNG, TGFB1, and EDN1 as critical targets, with IFNG demonstrating diagnostic potential through GEO dataset validation. The integration of GSEA with network pharmacology highlighted the therapeutic significance of the relaxin, osteoclast differentiation, HIF-1, and AGE-RAGE signaling pathways in QJJP decoction’s action. Mendelian randomization analysis indicated a positive causal relationship between IBD and AS, pinpointing rs2193041 as a key SNP influencing IFNG. Conclusion. Based on the principle of “treating different diseases with the same method” in traditional Chinese medicine theory, we explored the intricate mechanisms through which QJJP decoction addresses AS and IBD comorbidity. Our research spotlighted the pivotal role of the IFNG gene. IFNG emerges not only as a key therapeutic target but also assumes significance as a potential diagnostic biomarker through its genetic underpinnings. This investigation establishes a solid base for subsequent experimental inquiries. Our findings introduce novel approaches for incorporating traditional Chinese medicine into the treatment of AS-IBD comorbidity, setting the stage for groundbreaking research directions.

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Section: Discussionmentioning

confidence: 99%

The Mechanism of “Treating Different Diseases with the Same Treatment” by Qiangji Jianpi Decoction in Ankylosing Spondylitis Combined with Inflammatory Bowel Disease: A Comprehensive Analysis of Multiple Methods

Zhang,

Zhou,

Qian

2024

Gastroenterology Research and Practice

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“…Ankylosing spondylitis and inflammatory bowel disease are systemic, progressive, and recurrent chronic diseases [ 25 , 26 ]. According to epidemiology, the incidence of both diseases is increasing [ 2 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

Zhang

Chen

Qian

et al. 2023

Computational and Mathematical Methods in Medicine

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Background. Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are both autoimmune diseases, and they often occur together in clinical practice, but the pathogenesis is unclear. This study is aimed at identifying the hub genes and explore the related immune molecular mechanisms between AS and IBD by bioinformatics analysis. Methods. From the public Gene Expression Omnibus (GEO) database, the AS and IBD datasets (GSE73754, GSE59071, GSE25101, and GSE36807) were obtained. The immune cell infiltration in the peripheral blood tissues of GSE73754 and GSE59071 was assessed using the CIBERSORT algorithm. Then, we used the Weighted Gene Coexpression Network Analysis (WGCNA) to identify the Differentially Expressed Genes (DEGs) related to AS and IBD. Then, the immune genes from the ImmPort database intersected with the DEGs to obtain hub genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the functional correlation of hub genes. Then, hub genes were verified in GSE25101 and GSE36807. The clusterProfiler software and Gene Set Enrichment Analysis (GSEA) were used to conduct functional enrichment and pathway enrichment studies. Finally, the diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results. The analysis of immune characteristics showed that both AS and IBD were related to immunity, and neutrophils were positively correlated in both diseases. Nine coexpressed genes, including FCGRT, S100A11, IFNGR1, NFKBIZ, JAK2, LYN, PLAUR, ADM, and IL1RN, were linked to immune cells. The GO and KEGG analyses results showed that enrichment analysis was mainly related to cell transport and migration. Finally, the ROC curve was verified with the validation set, and it was found that PLAUR has clinical diagnostic significance and the most excellent specificity and sensitivity, respectively. Conclusions. PLAUR (uPAR) is a promising biomarker and will be an underlying genetic biomarker for diagnosing AS comorbid IBD. Inflammation and immunological modulation mediated by neutrophil infiltration were important in the development of AS and IBD and may be diagnostic and therapeutic targets.

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Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Pediatric Crohn's Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE73374 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE73374 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.

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Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration

Cited by 3 publications

References 66 publications

The Mechanism of “Treating Different Diseases with the Same Treatment” by Qiangji Jianpi Decoction in Ankylosing Spondylitis Combined with Inflammatory Bowel Disease: A Comprehensive Analysis of Multiple Methods

The Mechanism of “Treating Different Diseases with the Same Treatment” by Qiangji Jianpi Decoction in Ankylosing Spondylitis Combined with Inflammatory Bowel Disease: A Comprehensive Analysis of Multiple Methods

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

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