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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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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. |
format | Online Article Text |
id | pubmed-10274304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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