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Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy

Immunotherapy based on immune checkpoint inhibitors (ICIs) have demonstrated remarkable survival benefits and gained regulatory approval in non-small cell lung cancer (NSCLC) patients without an actionable driver mutation, but currently there is no well-established standard for how to screen the mos...

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Autores principales: Zhu, Mingyu, Zhang, Lu, Cui, Haiyan, Zhao, Qiang, Wang, Hao, Zhai, Baochao, Jiang, Richeng, Jiang, Zhansheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770854/
https://www.ncbi.nlm.nih.gov/pubmed/35069585
http://dx.doi.org/10.3389/fimmu.2021.800951
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author Zhu, Mingyu
Zhang, Lu
Cui, Haiyan
Zhao, Qiang
Wang, Hao
Zhai, Baochao
Jiang, Richeng
Jiang, Zhansheng
author_facet Zhu, Mingyu
Zhang, Lu
Cui, Haiyan
Zhao, Qiang
Wang, Hao
Zhai, Baochao
Jiang, Richeng
Jiang, Zhansheng
author_sort Zhu, Mingyu
collection PubMed
description Immunotherapy based on immune checkpoint inhibitors (ICIs) have demonstrated remarkable survival benefits and gained regulatory approval in non-small cell lung cancer (NSCLC) patients without an actionable driver mutation, but currently there is no well-established standard for how to screen the most suitable population for ICIs treatment. Here, we conducted a comprehensive analysis of the somatic mutation landscape of lung adenocarcinoma (LUAD) samples. After the stepwise screening of high-frequency mutated genes, two genes with prominent significance, FAT3 and LRP1B, were finally screened out. Through further analysis, we discovered that the co-mutation of FAT3 and LRP1B was associated with an earlier age of onset and occurred more frequently in Black/African American. Furthermore, co-mutation defines a unique subgroup of lung adenocarcinoma that can increase tumor mutational burden (TMB), boost cytotoxicity and tumor immunogenicity, and facilitate lymphocyte infiltration. The results of gene set enrichment analysis (GSEA) indicated that co-mutation can influence tumorigenesis through a variety of mechanisms. More strikingly, the subset of LUAD with co-mutation of FAT3 and LRP1B exhibited significantly prolonged immunotherapy progression free survival (PFS). In summary, co-mutation of FAT3 and LRP1B is a promising useful biomarker for predicting the efficacy of immunotherapy, which can improve the clinical efficiency of practicing precision medicine in lung adenocarcinoma patients.
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spelling pubmed-87708542022-01-21 Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy Zhu, Mingyu Zhang, Lu Cui, Haiyan Zhao, Qiang Wang, Hao Zhai, Baochao Jiang, Richeng Jiang, Zhansheng Front Immunol Immunology Immunotherapy based on immune checkpoint inhibitors (ICIs) have demonstrated remarkable survival benefits and gained regulatory approval in non-small cell lung cancer (NSCLC) patients without an actionable driver mutation, but currently there is no well-established standard for how to screen the most suitable population for ICIs treatment. Here, we conducted a comprehensive analysis of the somatic mutation landscape of lung adenocarcinoma (LUAD) samples. After the stepwise screening of high-frequency mutated genes, two genes with prominent significance, FAT3 and LRP1B, were finally screened out. Through further analysis, we discovered that the co-mutation of FAT3 and LRP1B was associated with an earlier age of onset and occurred more frequently in Black/African American. Furthermore, co-mutation defines a unique subgroup of lung adenocarcinoma that can increase tumor mutational burden (TMB), boost cytotoxicity and tumor immunogenicity, and facilitate lymphocyte infiltration. The results of gene set enrichment analysis (GSEA) indicated that co-mutation can influence tumorigenesis through a variety of mechanisms. More strikingly, the subset of LUAD with co-mutation of FAT3 and LRP1B exhibited significantly prolonged immunotherapy progression free survival (PFS). In summary, co-mutation of FAT3 and LRP1B is a promising useful biomarker for predicting the efficacy of immunotherapy, which can improve the clinical efficiency of practicing precision medicine in lung adenocarcinoma patients. Frontiers Media S.A. 2022-01-06 /pmc/articles/PMC8770854/ /pubmed/35069585 http://dx.doi.org/10.3389/fimmu.2021.800951 Text en Copyright © 2022 Zhu, Zhang, Cui, Zhao, Wang, Zhai, Jiang and Jiang 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 Immunology
Zhu, Mingyu
Zhang, Lu
Cui, Haiyan
Zhao, Qiang
Wang, Hao
Zhai, Baochao
Jiang, Richeng
Jiang, Zhansheng
Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title_full Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title_fullStr Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title_full_unstemmed Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title_short Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
title_sort co-mutation of fat3 and lrp1b in lung adenocarcinoma defines a unique subset correlated with the efficacy of immunotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770854/
https://www.ncbi.nlm.nih.gov/pubmed/35069585
http://dx.doi.org/10.3389/fimmu.2021.800951
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