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Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy

Immune checkpoint inhibitors (ICIs) significantly improve the survival of patients with non-small-cell lung cancer (NSCLC), but only some patients obtain clinical benefits. Predictive biomarkers for ICIs can accurately identify people who will benefit from immunotherapy. Lipid metabolism signaling p...

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Autores principales: Cheng, Tianli, Zhang, Jing, Liu, Danni, Lai, Guorong, Wen, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317604/
https://www.ncbi.nlm.nih.gov/pubmed/34335679
http://dx.doi.org/10.3389/fgene.2021.646362
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author Cheng, Tianli
Zhang, Jing
Liu, Danni
Lai, Guorong
Wen, Xiaoping
author_facet Cheng, Tianli
Zhang, Jing
Liu, Danni
Lai, Guorong
Wen, Xiaoping
author_sort Cheng, Tianli
collection PubMed
description Immune checkpoint inhibitors (ICIs) significantly improve the survival of patients with non-small-cell lung cancer (NSCLC), but only some patients obtain clinical benefits. Predictive biomarkers for ICIs can accurately identify people who will benefit from immunotherapy. Lipid metabolism signaling plays a key role in the tumor microenvironment (TME) and immunotherapy. Hence, we aimed to explore the association between the mutation status of the lipid metabolism pathway and the prognosis of patients with NSCLC treated with ICIs. We downloaded the mutation data and clinical data of a cohort of patients with NSCLC who received ICIs. Univariate and multivariate Cox regression models were used to analyze the association between the mutation status of the lipid metabolism signaling and the prognosis of NSCLC receiving ICIs. Additionally, The Cancer Genome Atlas (TCGA)–NSCLC cohort was used to explore the relationships between the different mutation statuses of lipid metabolism pathways and the TME. Additionally, we found that patients with high numbers of mutations in the lipid metabolism pathway had significantly enriched macrophages (M0- and M1-type), CD4 + T cells (activated memory), CD8 + T cells, Tfh cells and gamma delta T cells, significantly increased expression of inflammatory genes [interferon-γ (IFNG), CD8A, GZMA, GZMB, CXCL9, and CXCL10] and enhanced immunogenic factors [neoantigen loads (NALs), tumor mutation burden (TMB), and DNA damage repair pathways]. In the local-NSCLC cohort, we found that the group with a high number of mutations had a significantly higher tumor mutation burden (TMB) and PD-L1 expression. High mutation status in the lipid metabolism pathway is associated with significantly prolonged progression-free survival (PFS) in NSCLC, indicating that this marker can be used as a predictive indicator for patients with NSCLC receiving ICIs.
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spelling pubmed-83176042021-07-29 Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy Cheng, Tianli Zhang, Jing Liu, Danni Lai, Guorong Wen, Xiaoping Front Genet Genetics Immune checkpoint inhibitors (ICIs) significantly improve the survival of patients with non-small-cell lung cancer (NSCLC), but only some patients obtain clinical benefits. Predictive biomarkers for ICIs can accurately identify people who will benefit from immunotherapy. Lipid metabolism signaling plays a key role in the tumor microenvironment (TME) and immunotherapy. Hence, we aimed to explore the association between the mutation status of the lipid metabolism pathway and the prognosis of patients with NSCLC treated with ICIs. We downloaded the mutation data and clinical data of a cohort of patients with NSCLC who received ICIs. Univariate and multivariate Cox regression models were used to analyze the association between the mutation status of the lipid metabolism signaling and the prognosis of NSCLC receiving ICIs. Additionally, The Cancer Genome Atlas (TCGA)–NSCLC cohort was used to explore the relationships between the different mutation statuses of lipid metabolism pathways and the TME. Additionally, we found that patients with high numbers of mutations in the lipid metabolism pathway had significantly enriched macrophages (M0- and M1-type), CD4 + T cells (activated memory), CD8 + T cells, Tfh cells and gamma delta T cells, significantly increased expression of inflammatory genes [interferon-γ (IFNG), CD8A, GZMA, GZMB, CXCL9, and CXCL10] and enhanced immunogenic factors [neoantigen loads (NALs), tumor mutation burden (TMB), and DNA damage repair pathways]. In the local-NSCLC cohort, we found that the group with a high number of mutations had a significantly higher tumor mutation burden (TMB) and PD-L1 expression. High mutation status in the lipid metabolism pathway is associated with significantly prolonged progression-free survival (PFS) in NSCLC, indicating that this marker can be used as a predictive indicator for patients with NSCLC receiving ICIs. Frontiers Media S.A. 2021-07-14 /pmc/articles/PMC8317604/ /pubmed/34335679 http://dx.doi.org/10.3389/fgene.2021.646362 Text en Copyright © 2021 Cheng, Zhang, Liu, Lai and Wen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Cheng, Tianli
Zhang, Jing
Liu, Danni
Lai, Guorong
Wen, Xiaoping
Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title_full Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title_fullStr Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title_full_unstemmed Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title_short Prognosis of Non-small-cell Lung Cancer Patients With Lipid Metabolism Pathway Alternations to Immunotherapy
title_sort prognosis of non-small-cell lung cancer patients with lipid metabolism pathway alternations to immunotherapy
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317604/
https://www.ncbi.nlm.nih.gov/pubmed/34335679
http://dx.doi.org/10.3389/fgene.2021.646362
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