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Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with poor prognosis. Fatty acid metabolism is associated with cancer progression and a poor prognosis. We searched for long noncoding RNAs (lncRNAs) associated with fatty acid metabolism to predict the overall survival (OS) of pat...

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Autores principales: Wang, Helin, Cui, Junwei, Yu, Jian, Huang, Jian, Li, Mingying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023759/
https://www.ncbi.nlm.nih.gov/pubmed/35464865
http://dx.doi.org/10.3389/fgene.2022.855940
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author Wang, Helin
Cui, Junwei
Yu, Jian
Huang, Jian
Li, Mingying
author_facet Wang, Helin
Cui, Junwei
Yu, Jian
Huang, Jian
Li, Mingying
author_sort Wang, Helin
collection PubMed
description Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with poor prognosis. Fatty acid metabolism is associated with cancer progression and a poor prognosis. We searched for long noncoding RNAs (lncRNAs) associated with fatty acid metabolism to predict the overall survival (OS) of patients with LUAD. We obtained lncRNA expression profiles and clinical follow-up data related to fatty acid metabolism in patients with LUAD from The Cancer Genome Atlas and Molecular Signatures database. Patients were randomly divided into training, experimental, and combination groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression models were used to construct fatty acid metabolism-related prognostic markers, Kaplan-Meier analysis was used to compare the prognosis of each group, and receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the prognostic model. We used the pRRophetic algorithm to assess the treatment response based on the half-maximal inhibitory concentration (IC50) of each sample in the Genomics of Cancer Drug Sensitivity (GDSC) database. A fatty acid metabolism-related prognostic marker containing seven lncRNAs was constructed to predict OS in LUAD. In the training, test and combination groups, the patients were divided into high- and low-risk groups according to a formula. K–M analysis showed that patients in the high-risk group had poorer prognosis, with significant differences in the subgroup analysis. ROC analysis showed that the predictive ability of the model was more accurate. A clinical prediction nomogram combining lncRNA and clinical features was constructed to accurately predict OS and had high clinical application value. Therapeutics were screened based on the IC50 values of each sample in the GDSC database. We found that A.443654, AUY922, AZ628, A.770041, AZD.0530, AMG.706, and AG.014699 were more effective in high-risk patients. We constructed a 7-lncRNA prognostic model to predict the OS of patients with LUAD. In addition, the predictive nomogram model based on our established seven fatty acid metabolism-related lncRNA signatures provides better clinical value than that of the traditional TNM staging system in predicting the prognosis of patients with LUAD and presents new insights for personalized treatment.
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spelling pubmed-90237592022-04-23 Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma Wang, Helin Cui, Junwei Yu, Jian Huang, Jian Li, Mingying Front Genet Genetics Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with poor prognosis. Fatty acid metabolism is associated with cancer progression and a poor prognosis. We searched for long noncoding RNAs (lncRNAs) associated with fatty acid metabolism to predict the overall survival (OS) of patients with LUAD. We obtained lncRNA expression profiles and clinical follow-up data related to fatty acid metabolism in patients with LUAD from The Cancer Genome Atlas and Molecular Signatures database. Patients were randomly divided into training, experimental, and combination groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression models were used to construct fatty acid metabolism-related prognostic markers, Kaplan-Meier analysis was used to compare the prognosis of each group, and receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the prognostic model. We used the pRRophetic algorithm to assess the treatment response based on the half-maximal inhibitory concentration (IC50) of each sample in the Genomics of Cancer Drug Sensitivity (GDSC) database. A fatty acid metabolism-related prognostic marker containing seven lncRNAs was constructed to predict OS in LUAD. In the training, test and combination groups, the patients were divided into high- and low-risk groups according to a formula. K–M analysis showed that patients in the high-risk group had poorer prognosis, with significant differences in the subgroup analysis. ROC analysis showed that the predictive ability of the model was more accurate. A clinical prediction nomogram combining lncRNA and clinical features was constructed to accurately predict OS and had high clinical application value. Therapeutics were screened based on the IC50 values of each sample in the GDSC database. We found that A.443654, AUY922, AZ628, A.770041, AZD.0530, AMG.706, and AG.014699 were more effective in high-risk patients. We constructed a 7-lncRNA prognostic model to predict the OS of patients with LUAD. In addition, the predictive nomogram model based on our established seven fatty acid metabolism-related lncRNA signatures provides better clinical value than that of the traditional TNM staging system in predicting the prognosis of patients with LUAD and presents new insights for personalized treatment. Frontiers Media S.A. 2022-04-08 /pmc/articles/PMC9023759/ /pubmed/35464865 http://dx.doi.org/10.3389/fgene.2022.855940 Text en Copyright © 2022 Wang, Cui, Yu, Huang and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wang, Helin
Cui, Junwei
Yu, Jian
Huang, Jian
Li, Mingying
Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title_full Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title_fullStr Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title_full_unstemmed Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title_short Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma
title_sort identification of fatty acid metabolism-related lncrnas as biomarkers for clinical prognosis and immunotherapy response in patients with lung adenocarcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023759/
https://www.ncbi.nlm.nih.gov/pubmed/35464865
http://dx.doi.org/10.3389/fgene.2022.855940
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