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Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma
The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationshi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618567/ https://www.ncbi.nlm.nih.gov/pubmed/37907595 http://dx.doi.org/10.1038/s41698-023-00465-x |
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author | Feng, Juan Lan, Yang Liu, Feng Yuan, Ye Ge, Jia Wei, Sen Luo, Hu Li, Jianjun Luo, Tao Bian, Xiuwu |
author_facet | Feng, Juan Lan, Yang Liu, Feng Yuan, Ye Ge, Jia Wei, Sen Luo, Hu Li, Jianjun Luo, Tao Bian, Xiuwu |
author_sort | Feng, Juan |
collection | PubMed |
description | The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P < 0.001; validation cohort, HR = 6.47, P < 0.001; progression-free survival, HR = 4.76, P < 0.001). Our study revealed the prognostic value of the GI/HRD score in lung adenocarcinoma, but not for all lung cancer. Moreover, the combination of the GI/HRD score and TP53 status could be a promising strategy to predict the prognosis of patients with lung adenocarcinoma. |
format | Online Article Text |
id | pubmed-10618567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106185672023-11-02 Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma Feng, Juan Lan, Yang Liu, Feng Yuan, Ye Ge, Jia Wei, Sen Luo, Hu Li, Jianjun Luo, Tao Bian, Xiuwu NPJ Precis Oncol Article The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P < 0.001; validation cohort, HR = 6.47, P < 0.001; progression-free survival, HR = 4.76, P < 0.001). Our study revealed the prognostic value of the GI/HRD score in lung adenocarcinoma, but not for all lung cancer. Moreover, the combination of the GI/HRD score and TP53 status could be a promising strategy to predict the prognosis of patients with lung adenocarcinoma. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10618567/ /pubmed/37907595 http://dx.doi.org/10.1038/s41698-023-00465-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Feng, Juan Lan, Yang Liu, Feng Yuan, Ye Ge, Jia Wei, Sen Luo, Hu Li, Jianjun Luo, Tao Bian, Xiuwu Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title_full | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title_fullStr | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title_full_unstemmed | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title_short | Combination of genomic instability score and TP53 status for prognosis prediction in lung adenocarcinoma |
title_sort | combination of genomic instability score and tp53 status for prognosis prediction in lung adenocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618567/ https://www.ncbi.nlm.nih.gov/pubmed/37907595 http://dx.doi.org/10.1038/s41698-023-00465-x |
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