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Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort

BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, w...

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Autores principales: Zheng, Peng-Fei, Zou, Qiong-Chao, Chen, Lu-Zhu, Liu, Peng, Liu, Zheng-Yu, Pan, Hong-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306178/
https://www.ncbi.nlm.nih.gov/pubmed/35864510
http://dx.doi.org/10.1186/s12967-022-03517-1
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author Zheng, Peng-Fei
Zou, Qiong-Chao
Chen, Lu-Zhu
Liu, Peng
Liu, Zheng-Yu
Pan, Hong-Wei
author_facet Zheng, Peng-Fei
Zou, Qiong-Chao
Chen, Lu-Zhu
Liu, Peng
Liu, Zheng-Yu
Pan, Hong-Wei
author_sort Zheng, Peng-Fei
collection PubMed
description BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein–protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03517-1.
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spelling pubmed-93061782022-07-23 Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort Zheng, Peng-Fei Zou, Qiong-Chao Chen, Lu-Zhu Liu, Peng Liu, Zheng-Yu Pan, Hong-Wei J Transl Med Research BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein–protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03517-1. BioMed Central 2022-07-21 /pmc/articles/PMC9306178/ /pubmed/35864510 http://dx.doi.org/10.1186/s12967-022-03517-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zheng, Peng-Fei
Zou, Qiong-Chao
Chen, Lu-Zhu
Liu, Peng
Liu, Zheng-Yu
Pan, Hong-Wei
Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title_full Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title_fullStr Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title_full_unstemmed Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title_short Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
title_sort identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306178/
https://www.ncbi.nlm.nih.gov/pubmed/35864510
http://dx.doi.org/10.1186/s12967-022-03517-1
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