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Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis

Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we us...

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Autores principales: He, Tianzhen, Wang, Kai, Zhao, Peng, Zhu, Guanqun, Yin, Xinbao, Zhang, Yulian, Zhang, Zongliang, Zhao, Kai, Wang, Zhenlin, Wang, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804607/
https://www.ncbi.nlm.nih.gov/pubmed/34939750
http://dx.doi.org/10.1002/2211-5463.13357
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author He, Tianzhen
Wang, Kai
Zhao, Peng
Zhu, Guanqun
Yin, Xinbao
Zhang, Yulian
Zhang, Zongliang
Zhao, Kai
Wang, Zhenlin
Wang, Ke
author_facet He, Tianzhen
Wang, Kai
Zhao, Peng
Zhu, Guanqun
Yin, Xinbao
Zhang, Yulian
Zhang, Zongliang
Zhao, Kai
Wang, Zhenlin
Wang, Ke
author_sort He, Tianzhen
collection PubMed
description Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we used bioinformatic analyses, including machine learning algorithms, cell type deconvolution methods, and pathway enrichment methods. In this study, we identified 216 differentially expressed mRNAs (DEMs), of which 153 were upregulated, and 63 were downregulated genes. DEMs were mainly enriched in infiltrating neutrophils and regulation of leukocyte migration. Moreover, eight candidate biomarkers, DPP10, MST1L, DPP10‐AS1, CEP55, ACSL1, MGP, OLFM4, and SGK1, were identified. Of these candidate biomarkers, MST1L, OLFM4, and DPP10 were then validated in the GSE48958 dataset and were predicted to be strongly correlated with infiltrating immune cells of ulcerative colitis. The underlying mechanism of these key genes in the development of colitis was also predicted by gene set variation analysis. To further validate these biomarkers' expression in ulcerative colitis, we determined mRNA levels of SGK1, CEP55, ACSL1, OLFM4, and DPP10 in lipopolysaccharides (LPS)‐stimulated Raw264.7 cells by quantitative reverse transcription‐polymerase chain reaction. We also examined SGK1, CEP55, ACSL1, OLFM4, DPP10, and MGP expression in the colon tissues of dextran sodium sulfate‐induced colitis mice. Consistent with the predicted computational results, the mRNA levels of these candidate genes were markedly changed in LPS‐stimulated Raw264.7 cells and inflamed colon tissues. Hence, our findings indicated that these critical genes may act as diagnostic biomarkers for ulcerative colitis and that differential immune infiltration cells may help illustrate the progression of ulcerative colitis.
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spelling pubmed-88046072022-02-04 Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis He, Tianzhen Wang, Kai Zhao, Peng Zhu, Guanqun Yin, Xinbao Zhang, Yulian Zhang, Zongliang Zhao, Kai Wang, Zhenlin Wang, Ke FEBS Open Bio Research Articles Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we used bioinformatic analyses, including machine learning algorithms, cell type deconvolution methods, and pathway enrichment methods. In this study, we identified 216 differentially expressed mRNAs (DEMs), of which 153 were upregulated, and 63 were downregulated genes. DEMs were mainly enriched in infiltrating neutrophils and regulation of leukocyte migration. Moreover, eight candidate biomarkers, DPP10, MST1L, DPP10‐AS1, CEP55, ACSL1, MGP, OLFM4, and SGK1, were identified. Of these candidate biomarkers, MST1L, OLFM4, and DPP10 were then validated in the GSE48958 dataset and were predicted to be strongly correlated with infiltrating immune cells of ulcerative colitis. The underlying mechanism of these key genes in the development of colitis was also predicted by gene set variation analysis. To further validate these biomarkers' expression in ulcerative colitis, we determined mRNA levels of SGK1, CEP55, ACSL1, OLFM4, and DPP10 in lipopolysaccharides (LPS)‐stimulated Raw264.7 cells by quantitative reverse transcription‐polymerase chain reaction. We also examined SGK1, CEP55, ACSL1, OLFM4, DPP10, and MGP expression in the colon tissues of dextran sodium sulfate‐induced colitis mice. Consistent with the predicted computational results, the mRNA levels of these candidate genes were markedly changed in LPS‐stimulated Raw264.7 cells and inflamed colon tissues. Hence, our findings indicated that these critical genes may act as diagnostic biomarkers for ulcerative colitis and that differential immune infiltration cells may help illustrate the progression of ulcerative colitis. John Wiley and Sons Inc. 2022-01-12 /pmc/articles/PMC8804607/ /pubmed/34939750 http://dx.doi.org/10.1002/2211-5463.13357 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
He, Tianzhen
Wang, Kai
Zhao, Peng
Zhu, Guanqun
Yin, Xinbao
Zhang, Yulian
Zhang, Zongliang
Zhao, Kai
Wang, Zhenlin
Wang, Ke
Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title_full Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title_fullStr Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title_full_unstemmed Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title_short Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
title_sort integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804607/
https://www.ncbi.nlm.nih.gov/pubmed/34939750
http://dx.doi.org/10.1002/2211-5463.13357
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