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Co-occurring genomic alterations and immunotherapy efficacy in NSCLC
An oncogene-centric molecular classification paradigm in non-small cell lung cancer (NSCLC) has been established. Of note, the heterogeneity within each oncogenic driver-defined subgroup may be captured by co-occurring mutations, which potentially impact response/resistance to immune checkpoint inhi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766442/ https://www.ncbi.nlm.nih.gov/pubmed/35042953 http://dx.doi.org/10.1038/s41698-021-00243-7 |
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author | Zhang, Fan Wang, Jinliang Xu, Yu Cai, Shangli Li, Tao Wang, Guoqiang Li, Chengcheng Zhao, Lei Hu, Yi |
author_facet | Zhang, Fan Wang, Jinliang Xu, Yu Cai, Shangli Li, Tao Wang, Guoqiang Li, Chengcheng Zhao, Lei Hu, Yi |
author_sort | Zhang, Fan |
collection | PubMed |
description | An oncogene-centric molecular classification paradigm in non-small cell lung cancer (NSCLC) has been established. Of note, the heterogeneity within each oncogenic driver-defined subgroup may be captured by co-occurring mutations, which potentially impact response/resistance to immune checkpoint inhibitors (ICIs). We analyzed the data of 1745 NSCLCs and delineated the landscape of interaction effects of common co-mutations on ICI efficacy. Particularly in nonsquamous NSCLC, KRAS mutation remarkably interacted with its co-occurring mutations in TP53, STK11, PTPRD, RBM10, and ATM. Based on single mutation-based prediction models, adding interaction terms (referred to as inter-model) improved discriminative utilities in both training and validation sets. The scores of inter-models exhibited undifferentiated effectiveness regardless of tumor mutational burden and programmed death-ligand 1, and were identified as independent predictors for ICI benefit. Our work provides novel tools for patient selection and insights into NSCLC immunobiology, and highlights the advantage and necessity of considering interactions when developing prediction algorithms for cancer therapeutics. |
format | Online Article Text |
id | pubmed-8766442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87664422022-02-04 Co-occurring genomic alterations and immunotherapy efficacy in NSCLC Zhang, Fan Wang, Jinliang Xu, Yu Cai, Shangli Li, Tao Wang, Guoqiang Li, Chengcheng Zhao, Lei Hu, Yi NPJ Precis Oncol Article An oncogene-centric molecular classification paradigm in non-small cell lung cancer (NSCLC) has been established. Of note, the heterogeneity within each oncogenic driver-defined subgroup may be captured by co-occurring mutations, which potentially impact response/resistance to immune checkpoint inhibitors (ICIs). We analyzed the data of 1745 NSCLCs and delineated the landscape of interaction effects of common co-mutations on ICI efficacy. Particularly in nonsquamous NSCLC, KRAS mutation remarkably interacted with its co-occurring mutations in TP53, STK11, PTPRD, RBM10, and ATM. Based on single mutation-based prediction models, adding interaction terms (referred to as inter-model) improved discriminative utilities in both training and validation sets. The scores of inter-models exhibited undifferentiated effectiveness regardless of tumor mutational burden and programmed death-ligand 1, and were identified as independent predictors for ICI benefit. Our work provides novel tools for patient selection and insights into NSCLC immunobiology, and highlights the advantage and necessity of considering interactions when developing prediction algorithms for cancer therapeutics. Nature Publishing Group UK 2022-01-18 /pmc/articles/PMC8766442/ /pubmed/35042953 http://dx.doi.org/10.1038/s41698-021-00243-7 Text en © The Author(s) 2022 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 Zhang, Fan Wang, Jinliang Xu, Yu Cai, Shangli Li, Tao Wang, Guoqiang Li, Chengcheng Zhao, Lei Hu, Yi Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title | Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title_full | Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title_fullStr | Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title_full_unstemmed | Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title_short | Co-occurring genomic alterations and immunotherapy efficacy in NSCLC |
title_sort | co-occurring genomic alterations and immunotherapy efficacy in nsclc |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766442/ https://www.ncbi.nlm.nih.gov/pubmed/35042953 http://dx.doi.org/10.1038/s41698-021-00243-7 |
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