Identification of Novel Predictor Classifiers for Inflammatory Bowel Disease by Gene Expression Profiling

Montero‐Melendez, Trinidad; Llor, Xavier; García‐Planella, Esther; Perretti, Mauro; Suárez, Antonio

doi:10.1371/journal.pone.0076235

Cited by 69 publications

(40 citation statements)

References 23 publications

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“…(Supplementary Tables 9-10). In particular, 136 (UC) and 246 (CD) transcripts known to be involved in positive regulation of cytokine production were overexpressed in inflamed mucosa, including pathways for the production of IL-1, IL-2, IL-4, IL-6, IL-8/CXCL8, IL-10, IFNγ, and TNF, which were also upregulated in other IBD studies 29,30 . Furthermore, 118 (UC) and 118 (CD) transcripts were enriched for the defense response to other organisms, 51 (UC) and 108 (CD) transcripts were involved in the response to lipopolysaccharide, and 113 (UC) and 46 (CD) transcripts for the response to molecules of bacterial origin, all indicating a pathogenesis Fig.…”

Section: Inflammation-related Host Expression and In Vitro Validationmentioning

confidence: 83%

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

et al. 2020

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Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

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Section: Inflammation-related Host Expression and In Vitro Validationmentioning

confidence: 83%

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

et al. 2020

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“…Downstream of the MAPK and IκB‐NF‐κB pathways in activated mast cells, numerous transcription factors (e.g., Egr, NF‐κB, NFAT) are activated and direct de novo gene expression of cytokines and chemokines that direct the inflammatory events at the site, including immune cell recruitment and activation 56‐58 . Gene expression profiles are commonly recognized as a viable predictor in prognosis, severity, and survival in patients suffering from various inflammatory diseases including inflammatory bowel disease, 59 multiple myeloma, 60 and some cancers including esophageal squamous cell carcinoma and HPV associated tumors, 61,62 among many others. Previous research has measured TNF mRNA expression levels as an indicator for allergic inflammation severity in the airways 56 .…”

Section: Discussionmentioning

confidence: 99%

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

Watson

Maguire

Rouillard

et al. 2020

Journal of Leukocyte Biology

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Mast cells drive the inappropriate immune response characteristic of allergic inflammatory disorders via release of pro‐inflammatory mediators in response to environmental cues detected by the IgE‐FcεRI complex. The role of TGF‐β‐activated kinase 1 (TAK1), a participant in related signaling in other contexts, remains unknown in allergy. We detect novel activation of TAK1 at Ser412 in response to IgE‐mediated activation under SCF‐c‐kit potentiation in a mast cell‐driven response characteristic of allergic inflammation, which is potently blocked by TAK1 inhibitor 5Z‐7‐oxozeaenol (OZ). We, therefore, interrogated the role of TAK1 in a series of mast cell‐mediated responses using IgE‐sensitized murine bone marrow‐derived mast cells, stimulated with allergen under several TAK1 inhibition strategies. TAK1 inhibition by OZ resulted in significant impairment in the phosphorylation of MAPKs p38, ERK, and JNK; and mediation of the NF‐κB pathway via IκBα. Impaired gene expression and near abrogation in release of pro‐inflammatory cytokines TNF, IL‐6, IL‐13, and chemokines CCL1, and CCL2 was detected. Finally, a significant inhibition of mast cell degranulation, accompanied by an impairment in calcium mobilization, was observed in TAK1‐inhibited cells. These results suggest that TAK1 acts as a signaling node, not only linking the MAPK and NF‐κB pathways in driving the late‐phase response, but also initiation of the degranulation mechanism of the mast cell early‐phase response following allergen recognition and may warrant consideration in future therapeutic development.

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“…We firstly explored UC and CRC related data in Gene Expression Omnibus (GEO) and Array Express (AE) database, then screened these data with similar conditions (such as possessing normal controls, total RNA obtained from intestinal biopsies and clear sample descriptions), and finally six microarray expression profiles (GSE36807 [13], GSE38713 [14], GSE6731 [15], GSE4183 [16], GSE41258 [17] and E-MTAB-57 [18]) were selected. There were total 90 UC patients and 24 normal controls for UC analysis, while a total of 350 CRC patients and 140 normal controls were used.…”

Section: Methodsmentioning

confidence: 99%

Identification of genes in ulcerative colitis associated colorectal cancer based on centrality analysis of co-expression network

Zhu¹,

Li²,

Ji³

2015

neo

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PreviousColorectal cancer (CRC) is a well-recognized complication of Ulcerative colitis (UC) and patients with UC have a higher incidence of CRC than the general population. Early detection and mechanism of colitis-associated colorectal cancer (CAC) is still challenging. The aim of present study is to identify genes associated with CAC by centrality analysis of co-expression networks. Co-expression networks of CRC and UC were constructed by empirical Bayes approach based on top 200 gene signatures which identified by the model of genome-wide relative significance and genome-wide global significance across multiple datasets. Centrality of degree, stress centrality, betweenness centrality and closeness centrality of co-expression networks were selected to explore hub genes presented in CRC and UC. Validation of mRNA expression in CRC patients was conducted by real-time quantitative Polymerase Chain Reaction (qPCR). Pathway analysis was conducted based on Kyoto Encyclopedia of Genes and Genomes database. We found 21 common genes, such as SLC4A4 and AQP8, both existed in CRC and UC top 200 genes. By accessing centralities analyses of co-expression networks, HPGD and AQP8 were common hub genes in CRC and UC, and various centralities analyses of the same gene were not consistent. Patients with alteration of AQP8 have significantly reduced the survival rate according to real-time qPCR results. Our study displayed genes associated with CAC (AQP8 and HPGD), and they might be reliable biomarkers for early detection and therapies of CAC.

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Identification of Novel Predictor Classifiers for Inflammatory Bowel Disease by Gene Expression Profiling

Cited by 69 publications

References 23 publications

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation

Identification of genes in ulcerative colitis associated colorectal cancer based on centrality analysis of co-expression network

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