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Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis

BACKGROUND: Sepsis is a frequent complication in critically ill patients, is highly heterogeneous and is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA sequencing (RNA-Seq) to analyze biological pathways is widely used in clinical and molecula...

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Autores principales: Chen, I-Chieh, Chen, Hsin-Hua, Jiang, Yu-Han, Hsiao, Tzu-Hung, Ko, Tai-Ming, Chao, Wen-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951485/
https://www.ncbi.nlm.nih.gov/pubmed/36823620
http://dx.doi.org/10.1186/s12967-023-04002-z
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author Chen, I-Chieh
Chen, Hsin-Hua
Jiang, Yu-Han
Hsiao, Tzu-Hung
Ko, Tai-Ming
Chao, Wen-Cheng
author_facet Chen, I-Chieh
Chen, Hsin-Hua
Jiang, Yu-Han
Hsiao, Tzu-Hung
Ko, Tai-Ming
Chao, Wen-Cheng
author_sort Chen, I-Chieh
collection PubMed
description BACKGROUND: Sepsis is a frequent complication in critically ill patients, is highly heterogeneous and is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA sequencing (RNA-Seq) to analyze biological pathways is widely used in clinical and molecular genetic studies, but studies in elderly patients with sepsis are still lacking. Hence, we investigated the mortality-relevant biological features and transcriptomic features in elderly patients who were admitted to the intensive care unit (ICU) for sepsis. METHODS: We enrolled 37 elderly patients with sepsis from the ICU at Taichung Veterans General Hospital. On day-1 and day-8, clinical and laboratory data, as well as blood samples, were collected for RNA-Seq analysis. We identified the dynamic transcriptome and enriched pathways of differentially expressed genes between day-8 and day-1 through DVID enrichment analysis and Gene Set Enrichment Analysis. Then, the diversity of the T cell repertoire was analyzed with MiXCR. RESULTS: Overall, 37 patients had sepsis, and responders and non-responders were grouped through principal component analysis. Significantly higher SOFA scores at day-7, longer ventilator days, ICU lengths of stay and hospital mortality were found in the non-responder group, than in the responder group. On day-8 in elderly ICU patients with sepsis, genes related to innate immunity and inflammation, such as ZDHCC19, ALOX15, FCER1A, HDC, PRSS33, and PCSK9, were upregulated. The differentially expressed genes (DEGs) were enriched in the regulation of transcription, adaptive immune response, immunoglobulin production, negative regulation of transcription, and immune response. Moreover, there was a higher diversity of T-cell receptors on day-8 in the responder group, than on day-1, indicating that they had better regulated recovery from sepsis compared with the non-response patients. CONCLUSION: Sepsis mortality and incidence were both high in elderly individuals. We identified mortality-relevant biological features and transcriptomic features with functional pathway and MiXCR analyses based on RNA-Seq data; and found that the responder group had upregulated innate immunity and increased T cell diversity; compared with the non-responder group. RNA-Seq may be able to offer additional complementary information for the accurate and early prediction of treatment outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04002-z.
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spelling pubmed-99514852023-02-25 Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis Chen, I-Chieh Chen, Hsin-Hua Jiang, Yu-Han Hsiao, Tzu-Hung Ko, Tai-Ming Chao, Wen-Cheng J Transl Med Research BACKGROUND: Sepsis is a frequent complication in critically ill patients, is highly heterogeneous and is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA sequencing (RNA-Seq) to analyze biological pathways is widely used in clinical and molecular genetic studies, but studies in elderly patients with sepsis are still lacking. Hence, we investigated the mortality-relevant biological features and transcriptomic features in elderly patients who were admitted to the intensive care unit (ICU) for sepsis. METHODS: We enrolled 37 elderly patients with sepsis from the ICU at Taichung Veterans General Hospital. On day-1 and day-8, clinical and laboratory data, as well as blood samples, were collected for RNA-Seq analysis. We identified the dynamic transcriptome and enriched pathways of differentially expressed genes between day-8 and day-1 through DVID enrichment analysis and Gene Set Enrichment Analysis. Then, the diversity of the T cell repertoire was analyzed with MiXCR. RESULTS: Overall, 37 patients had sepsis, and responders and non-responders were grouped through principal component analysis. Significantly higher SOFA scores at day-7, longer ventilator days, ICU lengths of stay and hospital mortality were found in the non-responder group, than in the responder group. On day-8 in elderly ICU patients with sepsis, genes related to innate immunity and inflammation, such as ZDHCC19, ALOX15, FCER1A, HDC, PRSS33, and PCSK9, were upregulated. The differentially expressed genes (DEGs) were enriched in the regulation of transcription, adaptive immune response, immunoglobulin production, negative regulation of transcription, and immune response. Moreover, there was a higher diversity of T-cell receptors on day-8 in the responder group, than on day-1, indicating that they had better regulated recovery from sepsis compared with the non-response patients. CONCLUSION: Sepsis mortality and incidence were both high in elderly individuals. We identified mortality-relevant biological features and transcriptomic features with functional pathway and MiXCR analyses based on RNA-Seq data; and found that the responder group had upregulated innate immunity and increased T cell diversity; compared with the non-responder group. RNA-Seq may be able to offer additional complementary information for the accurate and early prediction of treatment outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04002-z. BioMed Central 2023-02-23 /pmc/articles/PMC9951485/ /pubmed/36823620 http://dx.doi.org/10.1186/s12967-023-04002-z Text en © The Author(s) 2023 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
Chen, I-Chieh
Chen, Hsin-Hua
Jiang, Yu-Han
Hsiao, Tzu-Hung
Ko, Tai-Ming
Chao, Wen-Cheng
Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title_full Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title_fullStr Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title_full_unstemmed Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title_short Whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
title_sort whole transcriptome analysis to explore the impaired immunological features in critically ill elderly patients with sepsis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951485/
https://www.ncbi.nlm.nih.gov/pubmed/36823620
http://dx.doi.org/10.1186/s12967-023-04002-z
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