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The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma

The epithelial-mesenchymal transition (EMT) process is tightly connected to tumors’ immune microenvironment. In colon adenocarcinoma (COAD), both the EMT and immune cell infiltration contribute to tumor progression; however, several questions regarding the mechanisms governing the interaction betwee...

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Autores principales: Heryanto, Yusri Dwi, Imoto, Seiya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603081/
https://www.ncbi.nlm.nih.gov/pubmed/37884639
http://dx.doi.org/10.1038/s41598-023-45792-y
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author Heryanto, Yusri Dwi
Imoto, Seiya
author_facet Heryanto, Yusri Dwi
Imoto, Seiya
author_sort Heryanto, Yusri Dwi
collection PubMed
description The epithelial-mesenchymal transition (EMT) process is tightly connected to tumors’ immune microenvironment. In colon adenocarcinoma (COAD), both the EMT and immune cell infiltration contribute to tumor progression; however, several questions regarding the mechanisms governing the interaction between EMT and the immune response remain unanswered. Our study aims to investigate the cross-talk between these two processes in cases of COAD and identify the key regulators involved. We utilized the EMT and immune signatures of samples from the COAD-TCGA database to identify three subtypes of COAD: high mesenchymal, medium mesenchymal, and low mesenchymal. We observed that EMT was associated with increased tumor immune response and infiltration mediated by pro-inflammatory cytokines. However, EMT was also linked to immunosuppressive activity that involved regulatory T cells, dendritic cells, and the upregulated expression of multiple immune checkpoints, such as PD-1, PDL-1, CTLA-4, and others. Finally, we employed the multivariate random forest feature importance method to identify key genes, such as DOK2 and MSRB3, that may play crucial roles in both EMT and the intratumoral immune response.
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spelling pubmed-106030812023-10-28 The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma Heryanto, Yusri Dwi Imoto, Seiya Sci Rep Article The epithelial-mesenchymal transition (EMT) process is tightly connected to tumors’ immune microenvironment. In colon adenocarcinoma (COAD), both the EMT and immune cell infiltration contribute to tumor progression; however, several questions regarding the mechanisms governing the interaction between EMT and the immune response remain unanswered. Our study aims to investigate the cross-talk between these two processes in cases of COAD and identify the key regulators involved. We utilized the EMT and immune signatures of samples from the COAD-TCGA database to identify three subtypes of COAD: high mesenchymal, medium mesenchymal, and low mesenchymal. We observed that EMT was associated with increased tumor immune response and infiltration mediated by pro-inflammatory cytokines. However, EMT was also linked to immunosuppressive activity that involved regulatory T cells, dendritic cells, and the upregulated expression of multiple immune checkpoints, such as PD-1, PDL-1, CTLA-4, and others. Finally, we employed the multivariate random forest feature importance method to identify key genes, such as DOK2 and MSRB3, that may play crucial roles in both EMT and the intratumoral immune response. Nature Publishing Group UK 2023-10-26 /pmc/articles/PMC10603081/ /pubmed/37884639 http://dx.doi.org/10.1038/s41598-023-45792-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Heryanto, Yusri Dwi
Imoto, Seiya
The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title_full The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title_fullStr The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title_full_unstemmed The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title_short The transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
title_sort transcriptome signature analysis of the epithelial-mesenchymal transition and immune cell infiltration in colon adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603081/
https://www.ncbi.nlm.nih.gov/pubmed/37884639
http://dx.doi.org/10.1038/s41598-023-45792-y
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