Evidence map›Paper›PMID 39977234›Full record

ArticleInflammatory bowel diseases2025

Novel Transcriptomic Signatures in Fibrostenotic Crohn's Disease: Dysregulated Pathways, Promising Biomarkers, and Putative Therapeutic Targets.

Animesh Acharjee, Uday Shivaji, Giovanni Santacroce, Sarah Akiror, Louisa Jeffery, Csilla Varnai, Gary Reynolds, Davide Zardo, Snehali Majumder, Asma Amamou and 3 more

Abstract readComparative Study
In one paragraph

Article in Inflammatory bowel diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Animesh AcharjeeInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Uday ShivajiGastroenterology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Giovanni SantacroceAPC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.ORCID 0000-0002-0544-0414
Sarah AkirorCentre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK.
Louisa JefferyInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Csilla VarnaiInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Gary ReynoldsCentre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK.
Davide ZardoDepartment of Pathology, San Bortolo Hospital, Vicenza, Italy.
Snehali MajumderInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Asma AmamouAPC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.
Georgios V GkoutosInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Marietta IacucciGastroenterology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.ORCID 0000-0002-3142-9550
Subrata GhoshAPC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.ORCID 0000-0002-1713-7797

Funding

University Hospitals Birmingham NHS Foundation Trust
6 · The paper itself

Abstract

backgroundFibrosis is a common complication in Crohn's disease (CD), often leading to intestinal strictures. This study aims to explore the transcriptomic signature of fibrostenotic ileal CD for a comprehensive characterization of biological and cellular mechanisms underlying intestinal fibrosis.

methodsNine CD patients undergoing surgery for fibrotic ileal strictures were prospectively recruited. RNA was extracted from fresh resected samples for bulk transcriptomics. Differentially expressed genes (DEGs) were identified (adj. P value < .05), and machine learning analyses were employed to compare gene expression patterns between strictures and non-strictured margins. Pathway enrichment analysis pinpointed relevant pathways. Furthermore, a random forest model was constructed to evaluate the significance of targeted genes. Relevant genes were subsequently validated through qPCR and further analyzed using a publicly available bulk RNA-seq dataset (GSE192786). Single-cell RNA sequencing (scRNA-seq) analysis was performed using the 10× Chromium Controller platform.

resultsBulk transcriptomics revealed unique transcriptomes with 81 DEGs, 64 significantly up-regulated, and 17 down-regulated in strictures compared to non-strictured margins. Up-regulated genes were mainly associated with inflammation, matrix and tissue remodeling, adipogenesis and cellular stress, while down-regulated genes were linked to epithelial barrier integrity. LY96, AKAP11, SRM, GREM1, EHD2, SERPINE1, HDAC1, and FGF2 showed high specificity for strictures. scRNA-seq linked up-regulated GREM1 exclusively to fibroblasts, while EHD2 and FGF2 showed upregulation in both fibroblasts and endothelial cells. LY96 and SRM were expressed by immune cells, whereas HDAC1, AKAP11, and SERPINE1 showed low expression across all cellular subsets.

conclusionsThis study comprehensively characterizes resected CD ileal strictures, elucidating main dysregulated pathways and identifying promising biomarkers and putative therapeutic targets.

Indexed as

Crohn DiseaseIleal DiseasesIleumTranscriptomeAdolescentAdultBiomarkersChildConstriction, PathologicFemaleFibrosisGene ExpressionGene Expression ProfilingHumansMaleMiddle AgedBiomarkersfibroblastimmune cellintestinal fibrosismachine learningsingle-cell transcriptomic

Identifiers

PMID39977234
PMCPMC12166298

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.