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Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer
BACKGROUND: Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare. METHODS: The nonnegative matri...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662860/ https://www.ncbi.nlm.nih.gov/pubmed/34893051 http://dx.doi.org/10.1186/s12885-021-09044-4 |
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author | Zheng, Yang Tang, Lili Liu, Ziling |
author_facet | Zheng, Yang Tang, Lili Liu, Ziling |
author_sort | Zheng, Yang |
collection | PubMed |
description | BACKGROUND: Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare. METHODS: The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis. RESULTS: Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed. CONCLUSIONS: Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09044-4. |
format | Online Article Text |
id | pubmed-8662860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86628602021-12-10 Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer Zheng, Yang Tang, Lili Liu, Ziling BMC Cancer Research BACKGROUND: Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare. METHODS: The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis. RESULTS: Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed. CONCLUSIONS: Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09044-4. BioMed Central 2021-12-10 /pmc/articles/PMC8662860/ /pubmed/34893051 http://dx.doi.org/10.1186/s12885-021-09044-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zheng, Yang Tang, Lili Liu, Ziling Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title | Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title_full | Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title_fullStr | Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title_full_unstemmed | Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title_short | Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
title_sort | multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662860/ https://www.ncbi.nlm.nih.gov/pubmed/34893051 http://dx.doi.org/10.1186/s12885-021-09044-4 |
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