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A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis

BACKGROUND AND AIMS: Ulcerative colitis [UC] is a complex heterogeneous disease. This study aims to reveal the underlying molecular features of UC using genome-scale transcriptomes of patients with UC, and to develop and validate a novel stratification scheme. METHODS: A normalised compendium was cr...

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Autores principales: Chang, Min-Jing, Hao, Jia-Wei, Qiao, Jun, Chen, Miao-Ran, Wang, Qian, Wang, Qi, Zhang, Sheng-Xiao, Yu, Qi, He, Pei-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274304/
https://www.ncbi.nlm.nih.gov/pubmed/36682023
http://dx.doi.org/10.1093/ecco-jcc/jjad011
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author Chang, Min-Jing
Hao, Jia-Wei
Qiao, Jun
Chen, Miao-Ran
Wang, Qian
Wang, Qi
Zhang, Sheng-Xiao
Yu, Qi
He, Pei-Feng
author_facet Chang, Min-Jing
Hao, Jia-Wei
Qiao, Jun
Chen, Miao-Ran
Wang, Qian
Wang, Qi
Zhang, Sheng-Xiao
Yu, Qi
He, Pei-Feng
author_sort Chang, Min-Jing
collection PubMed
description BACKGROUND AND AIMS: Ulcerative colitis [UC] is a complex heterogeneous disease. This study aims to reveal the underlying molecular features of UC using genome-scale transcriptomes of patients with UC, and to develop and validate a novel stratification scheme. METHODS: A normalised compendium was created using colon tissue samples (455 patients with UC and 147 healthy controls [HCs]), covering genes from 10 microarray datasets. Upregulated differentially expressed genes [DEGs] were subjected to functional network analysis, wherein samples were grouped using unsupervised clustering. Additionally, the robustness of subclustering was further assessed by two RNA sequencing datasets [100 patients with UC and 16 HCs]. Finally, the Xgboost classifier was applied to the independent datasets to evaluate the efficacy of different biologics in patients with UC. RESULTS: Based on 267 upregulated DEGs of the transcript profiles, UC patients were classified into three subtypes [subtypes A–C] with distinct molecular and cellular signatures. Epithelial activation-related pathways were significantly enriched in subtype A [named epithelial proliferation], whereas subtype C was characterised as the immune activation subtype with prominent immune cells and proinflammatory signatures. Subtype B [named mixed] was modestly activated in all the signalling pathways. Notably, subtype A showed a stronger association with the superior response of biologics such as golimumab, infliximab, vedolizumab, and ustekinumab compared with subtype C. CONCLUSIONS: We conducted a deep stratification of mucosal tissue using the most comprehensive microarray and RNA sequencing data, providing critical insights into pathophysiological features of UC, which could serve as a template for stratified treatment approaches.
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spelling pubmed-102743042023-06-17 A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis Chang, Min-Jing Hao, Jia-Wei Qiao, Jun Chen, Miao-Ran Wang, Qian Wang, Qi Zhang, Sheng-Xiao Yu, Qi He, Pei-Feng J Crohns Colitis Original Articles BACKGROUND AND AIMS: Ulcerative colitis [UC] is a complex heterogeneous disease. This study aims to reveal the underlying molecular features of UC using genome-scale transcriptomes of patients with UC, and to develop and validate a novel stratification scheme. METHODS: A normalised compendium was created using colon tissue samples (455 patients with UC and 147 healthy controls [HCs]), covering genes from 10 microarray datasets. Upregulated differentially expressed genes [DEGs] were subjected to functional network analysis, wherein samples were grouped using unsupervised clustering. Additionally, the robustness of subclustering was further assessed by two RNA sequencing datasets [100 patients with UC and 16 HCs]. Finally, the Xgboost classifier was applied to the independent datasets to evaluate the efficacy of different biologics in patients with UC. RESULTS: Based on 267 upregulated DEGs of the transcript profiles, UC patients were classified into three subtypes [subtypes A–C] with distinct molecular and cellular signatures. Epithelial activation-related pathways were significantly enriched in subtype A [named epithelial proliferation], whereas subtype C was characterised as the immune activation subtype with prominent immune cells and proinflammatory signatures. Subtype B [named mixed] was modestly activated in all the signalling pathways. Notably, subtype A showed a stronger association with the superior response of biologics such as golimumab, infliximab, vedolizumab, and ustekinumab compared with subtype C. CONCLUSIONS: We conducted a deep stratification of mucosal tissue using the most comprehensive microarray and RNA sequencing data, providing critical insights into pathophysiological features of UC, which could serve as a template for stratified treatment approaches. Oxford University Press 2023-01-22 /pmc/articles/PMC10274304/ /pubmed/36682023 http://dx.doi.org/10.1093/ecco-jcc/jjad011 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Chang, Min-Jing
Hao, Jia-Wei
Qiao, Jun
Chen, Miao-Ran
Wang, Qian
Wang, Qi
Zhang, Sheng-Xiao
Yu, Qi
He, Pei-Feng
A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title_full A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title_fullStr A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title_full_unstemmed A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title_short A Compendium of Mucosal Molecular Characteristics Provides Novel Perspectives on the Treatment of Ulcerative Colitis
title_sort compendium of mucosal molecular characteristics provides novel perspectives on the treatment of ulcerative colitis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274304/
https://www.ncbi.nlm.nih.gov/pubmed/36682023
http://dx.doi.org/10.1093/ecco-jcc/jjad011
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