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Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma
OBJECTIVE: Cuproptosis is a newly discovered copper-independent cell death modality, and limited evidence suggests the critical implications in human cancers. Nonetheless, the clinical impacts of cuproptosis-relevant lncRNAs in lung adenocarcinoma (LUAD) remain largely ill-defined. The present study...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587678/ https://www.ncbi.nlm.nih.gov/pubmed/36281357 http://dx.doi.org/10.1155/2022/2756611 |
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author | Wang, Zhuning Yao, Junqiao Dong, Tengyu Niu, Xing |
author_facet | Wang, Zhuning Yao, Junqiao Dong, Tengyu Niu, Xing |
author_sort | Wang, Zhuning |
collection | PubMed |
description | OBJECTIVE: Cuproptosis is a newly discovered copper-independent cell death modality, and limited evidence suggests the critical implications in human cancers. Nonetheless, the clinical impacts of cuproptosis-relevant lncRNAs in lung adenocarcinoma (LUAD) remain largely ill-defined. The present study was aimed at defining a cuproptosis-relevant lncRNA signature for LUAD and discuss the clinical utility. METHODS: We collected transcriptome expression profiling, clinical information, somatic mutation, and copy number variations from TCGA-LUAD cohort retrospectively. The genetic alterations of cuproptosis genes were systematically assessed across LUAD, and cuproptosis-relevant lncRNAs were screened for defining a LASSO prognostic model. Genomic alterations, immunological and stemness features, and therapeutic sensitivity were studied with a series of computational approaches. RESULTS: Cuproptosis genes displayed aberrant expression and widespread genomic alterations across LUAD, potentially modulated by m6A/m5C/m1A RNA modification mechanisms. We defined a cuproptosis-relevant lncRNA signature, with a reliable efficacy in predicting clinical outcomes. High-risk subset displayed higher somatic mutations, CNVs, TMB, SNV neoantigens, aneuploidy score, CTA score, homologous recombination defects, and intratumor heterogeneity, cytolytic activity, CD8+ T effector, and antigen processing machinery, proving that this subset might benefit from immunotherapy. Increased stemness indexes and activity of oncogenic pathways might contribute to undesirable prognostic outcomes for high-risk subset. Additionally, high-risk patients generally exhibited higher response to chemotherapeutic agents (cisplatin, etc.). We also predicted several small molecule compounds (GSK461364, KX2-391, etc.) for treating this subset. CONCLUSION: Accordingly, this cuproptosis-relevant lncRNA signature offers an efficient approach to identify and characterize diverse prognosis, genomic alterations, and treatment outcomes in LUAD, thus potentially assisting personalized therapy. |
format | Online Article Text |
id | pubmed-9587678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95876782022-10-23 Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma Wang, Zhuning Yao, Junqiao Dong, Tengyu Niu, Xing J Immunol Res Research Article OBJECTIVE: Cuproptosis is a newly discovered copper-independent cell death modality, and limited evidence suggests the critical implications in human cancers. Nonetheless, the clinical impacts of cuproptosis-relevant lncRNAs in lung adenocarcinoma (LUAD) remain largely ill-defined. The present study was aimed at defining a cuproptosis-relevant lncRNA signature for LUAD and discuss the clinical utility. METHODS: We collected transcriptome expression profiling, clinical information, somatic mutation, and copy number variations from TCGA-LUAD cohort retrospectively. The genetic alterations of cuproptosis genes were systematically assessed across LUAD, and cuproptosis-relevant lncRNAs were screened for defining a LASSO prognostic model. Genomic alterations, immunological and stemness features, and therapeutic sensitivity were studied with a series of computational approaches. RESULTS: Cuproptosis genes displayed aberrant expression and widespread genomic alterations across LUAD, potentially modulated by m6A/m5C/m1A RNA modification mechanisms. We defined a cuproptosis-relevant lncRNA signature, with a reliable efficacy in predicting clinical outcomes. High-risk subset displayed higher somatic mutations, CNVs, TMB, SNV neoantigens, aneuploidy score, CTA score, homologous recombination defects, and intratumor heterogeneity, cytolytic activity, CD8+ T effector, and antigen processing machinery, proving that this subset might benefit from immunotherapy. Increased stemness indexes and activity of oncogenic pathways might contribute to undesirable prognostic outcomes for high-risk subset. Additionally, high-risk patients generally exhibited higher response to chemotherapeutic agents (cisplatin, etc.). We also predicted several small molecule compounds (GSK461364, KX2-391, etc.) for treating this subset. CONCLUSION: Accordingly, this cuproptosis-relevant lncRNA signature offers an efficient approach to identify and characterize diverse prognosis, genomic alterations, and treatment outcomes in LUAD, thus potentially assisting personalized therapy. Hindawi 2022-10-14 /pmc/articles/PMC9587678/ /pubmed/36281357 http://dx.doi.org/10.1155/2022/2756611 Text en Copyright © 2022 Zhuning Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Zhuning Yao, Junqiao Dong, Tengyu Niu, Xing Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title | Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title_full | Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title_fullStr | Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title_full_unstemmed | Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title_short | Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma |
title_sort | definition of a novel cuproptosis-relevant lncrna signature for uncovering distinct survival, genomic alterations, and treatment implications in lung adenocarcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587678/ https://www.ncbi.nlm.nih.gov/pubmed/36281357 http://dx.doi.org/10.1155/2022/2756611 |
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