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Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma

The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from Th...

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Autores principales: Peng, Xinyi, Xia, Zhenqi, Guo, Yong, Li, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292897/
https://www.ncbi.nlm.nih.gov/pubmed/37279937
http://dx.doi.org/10.18632/aging.204770
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author Peng, Xinyi
Xia, Zhenqi
Guo, Yong
Li, Yan
author_facet Peng, Xinyi
Xia, Zhenqi
Guo, Yong
Li, Yan
author_sort Peng, Xinyi
collection PubMed
description The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from The Cancer Genome Atlas. By applying ESTIMATE and ssGSEA, KRAS-mutated group was discovered to be associated with lower immune infiltration, lower expression of immune checkpoints, especially, a lower abundance of B cell, CD8+ T cell, dendritic cell, natural killer cell, and macrophage, higher abundance of neutrophil and endothelial cell. Through ssGSEA, we found that the process of antigen-presenting cell co-inhibition and co-stimulation were inhibited, cytolytic activity and human leukocyte antigen molecules were downregulated in the KRAS-mutated group. And KRAS mutation is negatively related to antigen presentation and procession, cytotoxic lymphocyte activity, cytolytic activities, and cytokine interaction signaling pathway via gene function enrichment analysis. Finally, 24 immune-related genes were identified to establish an immune-related gene signature with excellent prognostic prediction capacity, whose 1-, 3- and 5-year AUCs were 0.893, 0.986, and 0.999. Our findings elucidate the features of the immune landscape of KRAS-mutated groups and successfully established a prognostic signature on the basis of immune-related genes in LUAD.
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spelling pubmed-102928972023-06-27 Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma Peng, Xinyi Xia, Zhenqi Guo, Yong Li, Yan Aging (Albany NY) Research Paper The heterogeneity of lung adenocarcinoma (LUAD) indicated that target therapies and immunotherapies may not be effective in all patients. The exploration of the feature of the immune landscape of different gene mutations may provide novel perspectives. In this study, we obtained LUAD samples from The Cancer Genome Atlas. By applying ESTIMATE and ssGSEA, KRAS-mutated group was discovered to be associated with lower immune infiltration, lower expression of immune checkpoints, especially, a lower abundance of B cell, CD8+ T cell, dendritic cell, natural killer cell, and macrophage, higher abundance of neutrophil and endothelial cell. Through ssGSEA, we found that the process of antigen-presenting cell co-inhibition and co-stimulation were inhibited, cytolytic activity and human leukocyte antigen molecules were downregulated in the KRAS-mutated group. And KRAS mutation is negatively related to antigen presentation and procession, cytotoxic lymphocyte activity, cytolytic activities, and cytokine interaction signaling pathway via gene function enrichment analysis. Finally, 24 immune-related genes were identified to establish an immune-related gene signature with excellent prognostic prediction capacity, whose 1-, 3- and 5-year AUCs were 0.893, 0.986, and 0.999. Our findings elucidate the features of the immune landscape of KRAS-mutated groups and successfully established a prognostic signature on the basis of immune-related genes in LUAD. Impact Journals 2023-06-06 /pmc/articles/PMC10292897/ /pubmed/37279937 http://dx.doi.org/10.18632/aging.204770 Text en Copyright: © 2023 Peng et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Peng, Xinyi
Xia, Zhenqi
Guo, Yong
Li, Yan
Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title_full Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title_fullStr Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title_full_unstemmed Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title_short Immune landscape and prognostic immune-related signature in KRAS-mutated lung adenocarcinoma
title_sort immune landscape and prognostic immune-related signature in kras-mutated lung adenocarcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292897/
https://www.ncbi.nlm.nih.gov/pubmed/37279937
http://dx.doi.org/10.18632/aging.204770
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