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Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma

PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency...

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Autores principales: Shang, Xueqian, Qi, Kang, Liu, Xiangzheng, Liu, Qinghao, Zhang, Xining, Wang, Dongliang, Huang, Weiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562462/
https://www.ncbi.nlm.nih.gov/pubmed/36249053
http://dx.doi.org/10.3389/fonc.2022.854999
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author Shang, Xueqian
Qi, Kang
Liu, Xiangzheng
Liu, Qinghao
Zhang, Xining
Wang, Dongliang
Huang, Weiming
author_facet Shang, Xueqian
Qi, Kang
Liu, Xiangzheng
Liu, Qinghao
Zhang, Xining
Wang, Dongliang
Huang, Weiming
author_sort Shang, Xueqian
collection PubMed
description PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency of these occurrences. Homologous recombination deficiency (HRD) was used to induce particular DNA aberration profiles and related transcriptome alterations. Their presence can identify whether an HR deficiency is present or absent in a particular tumor sample, even without observed HR gene changes. From whole-exome sequencing data in lung adenocarcinoma obtained from TCGA, we obtained several mutational signatures associated with HRD and determined that these HRD-associated mutational signatures are related to genomic installability. We then constructed a prediction model, which found that 11 genes associated with HRD scores could be used as predictors of survival outcomes in LUAD patients. These genes are related to PI3K-Akt, T cell receptors, and the Chemokine pathway. Other GEO datasets validated the survival prediction, which was independent of the PD1/PDL1 treatment. Collectively, our study provides transcriptome biomarkers of lung adenocarcinoma complementary to the HRD score and introduces a novel method of identifying prognostic biomarkers of immunotherapy.
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spelling pubmed-95624622022-10-15 Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma Shang, Xueqian Qi, Kang Liu, Xiangzheng Liu, Qinghao Zhang, Xining Wang, Dongliang Huang, Weiming Front Oncol Oncology PARP inhibitors can be used to treat solid tumors that often have mutations in important homologous recombination (HR) genes, such as BRCA1/2. While other kinds of tumors could also experience HR deficiencies, including those associated with lung cancer, there is little information on the frequency of these occurrences. Homologous recombination deficiency (HRD) was used to induce particular DNA aberration profiles and related transcriptome alterations. Their presence can identify whether an HR deficiency is present or absent in a particular tumor sample, even without observed HR gene changes. From whole-exome sequencing data in lung adenocarcinoma obtained from TCGA, we obtained several mutational signatures associated with HRD and determined that these HRD-associated mutational signatures are related to genomic installability. We then constructed a prediction model, which found that 11 genes associated with HRD scores could be used as predictors of survival outcomes in LUAD patients. These genes are related to PI3K-Akt, T cell receptors, and the Chemokine pathway. Other GEO datasets validated the survival prediction, which was independent of the PD1/PDL1 treatment. Collectively, our study provides transcriptome biomarkers of lung adenocarcinoma complementary to the HRD score and introduces a novel method of identifying prognostic biomarkers of immunotherapy. Frontiers Media S.A. 2022-09-30 /pmc/articles/PMC9562462/ /pubmed/36249053 http://dx.doi.org/10.3389/fonc.2022.854999 Text en Copyright © 2022 Shang, Qi, Liu, Liu, Zhang, Wang and Huang 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 Oncology
Shang, Xueqian
Qi, Kang
Liu, Xiangzheng
Liu, Qinghao
Zhang, Xining
Wang, Dongliang
Huang, Weiming
Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title_full Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title_fullStr Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title_full_unstemmed Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title_short Signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
title_sort signatures associated with homologous recombination deficiency and immune regulation to improve clinical outcomes in patients with lung adenocarcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562462/
https://www.ncbi.nlm.nih.gov/pubmed/36249053
http://dx.doi.org/10.3389/fonc.2022.854999
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