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Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer

BACKGROUND: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLC...

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Autores principales: Li, Ding, Wu, Xuan, Fan, Xinxin, Cheng, Cheng, Li, Dongbei, Zhang, Wenzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761144/
https://www.ncbi.nlm.nih.gov/pubmed/36544685
http://dx.doi.org/10.21037/atm-22-5294
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author Li, Ding
Wu, Xuan
Fan, Xinxin
Cheng, Cheng
Li, Dongbei
Zhang, Wenzhou
author_facet Li, Ding
Wu, Xuan
Fan, Xinxin
Cheng, Cheng
Li, Dongbei
Zhang, Wenzhou
author_sort Li, Ding
collection PubMed
description BACKGROUND: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLCA) remains poorly described. METHODS: We downloaded the transcriptome sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and lasso Cox regression analyses were performed to construct the prognostic risk signature, the predictive accuracy of which was validated in the subsequent independence and stratification analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the underlying molecular mechanisms involved in the signature to explore therapeutic vulnerabilities and potential targets in BLCA. Tumor mutational burden (TMB) and tumor immune dysfunction and exclusion (TIDE) were used to estimate the response to immune checkpoint inhibitors (ICIs). We further explored the potential new drug-target candidates based on the half maximal inhibitory concentration for this patient population. RESULTS: Fifteen cuproptosis-related lncRNAs significantly associated with survival were identified to construct the risk signature based on the normalized expression level and regression coefficient of each gene. The patients with BLCA and high-risk scores defined by the signature were associated with worse survival outcomes. The differentially expressed genes (DEGs) between the 2 risk groups had different biological activity. Furthermore, the patients in the low-risk group exhibited a higher TMB index and a lower TIDE score. The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score. CONCLUSIONS: Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population.
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spelling pubmed-97611442022-12-20 Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer Li, Ding Wu, Xuan Fan, Xinxin Cheng, Cheng Li, Dongbei Zhang, Wenzhou Ann Transl Med Original Article BACKGROUND: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLCA) remains poorly described. METHODS: We downloaded the transcriptome sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and lasso Cox regression analyses were performed to construct the prognostic risk signature, the predictive accuracy of which was validated in the subsequent independence and stratification analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the underlying molecular mechanisms involved in the signature to explore therapeutic vulnerabilities and potential targets in BLCA. Tumor mutational burden (TMB) and tumor immune dysfunction and exclusion (TIDE) were used to estimate the response to immune checkpoint inhibitors (ICIs). We further explored the potential new drug-target candidates based on the half maximal inhibitory concentration for this patient population. RESULTS: Fifteen cuproptosis-related lncRNAs significantly associated with survival were identified to construct the risk signature based on the normalized expression level and regression coefficient of each gene. The patients with BLCA and high-risk scores defined by the signature were associated with worse survival outcomes. The differentially expressed genes (DEGs) between the 2 risk groups had different biological activity. Furthermore, the patients in the low-risk group exhibited a higher TMB index and a lower TIDE score. The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score. CONCLUSIONS: Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population. AME Publishing Company 2022-11 /pmc/articles/PMC9761144/ /pubmed/36544685 http://dx.doi.org/10.21037/atm-22-5294 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Li, Ding
Wu, Xuan
Fan, Xinxin
Cheng, Cheng
Li, Dongbei
Zhang, Wenzhou
Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title_full Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title_fullStr Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title_full_unstemmed Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title_short Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer
title_sort comprehensive analysis of cuproptosis-related lncrnas in the prognosis and therapy response of patients with bladder cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9761144/
https://www.ncbi.nlm.nih.gov/pubmed/36544685
http://dx.doi.org/10.21037/atm-22-5294
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