Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma

Abstract Background Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated. Therefore, in the p...

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Main Authors: Fangwei Wang, Hongsheng Lin, Qisheng Su, Chaoqian Li
Format: Article
Language:English
Published: BMC 2022-09-01
Series:World Journal of Surgical Oncology
Subjects:
Online Access:https://doi.org/10.1186/s12957-022-02727-7
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author Fangwei Wang
Hongsheng Lin
Qisheng Su
Chaoqian Li
author_facet Fangwei Wang
Hongsheng Lin
Qisheng Su
Chaoqian Li
author_sort Fangwei Wang
collection DOAJ
description Abstract Background Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated. Therefore, in the present study, we aimed to investigate the role of cuproptosis-related lncRNA signature in clinical prognosis prediction and immunotherapy and the relationship with drug sensitivity. Material and methods Genomic and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and cuproptosis-related genes were obtained from cuproptosis-related studies. The prognostic signature was constructed by co-expression analysis and Cox regression analysis. Patients were divided into high and low risk groups, and then, a further series of model validations were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumor mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs, thereby identifying its sensitivity toward potential drugs for LUAD. Results A total of 16 cuproptosis-related lncRNAs were obtained, and a prognostic signature was developed. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. We also found that immune-related functions, such as antiviral activity, were suppressed in high-risk patients who had mutations in oncogenes. OS was poorer in patients with high TMB. TIDE algorithms showed that high-risk patients have a greater potential for immune escape and less effective immunotherapy. Conclusion To conclude, the 16 cuproptosis-related lncRNAs can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.
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spelling doaj.art-bb5471bbf30b4c1fa6aba761ee6dbae32022-12-22T04:05:01ZengBMCWorld Journal of Surgical Oncology1477-78192022-09-0120111610.1186/s12957-022-02727-7Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinomaFangwei Wang0Hongsheng Lin1Qisheng Su2Chaoqian Li3Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Guangxi Medical UniversityDepartment of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Background Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated. Therefore, in the present study, we aimed to investigate the role of cuproptosis-related lncRNA signature in clinical prognosis prediction and immunotherapy and the relationship with drug sensitivity. Material and methods Genomic and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and cuproptosis-related genes were obtained from cuproptosis-related studies. The prognostic signature was constructed by co-expression analysis and Cox regression analysis. Patients were divided into high and low risk groups, and then, a further series of model validations were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumor mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs, thereby identifying its sensitivity toward potential drugs for LUAD. Results A total of 16 cuproptosis-related lncRNAs were obtained, and a prognostic signature was developed. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. We also found that immune-related functions, such as antiviral activity, were suppressed in high-risk patients who had mutations in oncogenes. OS was poorer in patients with high TMB. TIDE algorithms showed that high-risk patients have a greater potential for immune escape and less effective immunotherapy. Conclusion To conclude, the 16 cuproptosis-related lncRNAs can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.https://doi.org/10.1186/s12957-022-02727-7CuproptosislncRNAsSignaturePrognosisImmuneDrug sensitivity
spellingShingle Fangwei Wang
Hongsheng Lin
Qisheng Su
Chaoqian Li
Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
World Journal of Surgical Oncology
Cuproptosis
lncRNAs
Signature
Prognosis
Immune
Drug sensitivity
title Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
title_full Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
title_fullStr Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
title_full_unstemmed Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
title_short Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma
title_sort cuproptosis related lncrna predict prognosis and immune response of lung adenocarcinoma
topic Cuproptosis
lncRNAs
Signature
Prognosis
Immune
Drug sensitivity
url https://doi.org/10.1186/s12957-022-02727-7
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AT qishengsu cuproptosisrelatedlncrnapredictprognosisandimmuneresponseoflungadenocarcinoma
AT chaoqianli cuproptosisrelatedlncrnapredictprognosisandimmuneresponseoflungadenocarcinoma