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Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma

BACKGROUND: The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear. METHODS...

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Autores principales: Yuan, Wei, Xiao, Jun-hao, Zhang, Jian-song, Mao, Ben-liang, Wang, Peng-zhen, Wang, Bai-lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086263/
https://www.ncbi.nlm.nih.gov/pubmed/37056336
http://dx.doi.org/10.3389/fonc.2023.1153353
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author Yuan, Wei
Xiao, Jun-hao
Zhang, Jian-song
Mao, Ben-liang
Wang, Peng-zhen
Wang, Bai-lin
author_facet Yuan, Wei
Xiao, Jun-hao
Zhang, Jian-song
Mao, Ben-liang
Wang, Peng-zhen
Wang, Bai-lin
author_sort Yuan, Wei
collection PubMed
description BACKGROUND: The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear. METHODS: Based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed. RESULTS: We constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks. CONCLUSIONS: We constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy.
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spelling pubmed-100862632023-04-12 Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma Yuan, Wei Xiao, Jun-hao Zhang, Jian-song Mao, Ben-liang Wang, Peng-zhen Wang, Bai-lin Front Oncol Oncology BACKGROUND: The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear. METHODS: Based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed. RESULTS: We constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks. CONCLUSIONS: We constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy. Frontiers Media S.A. 2023-03-28 /pmc/articles/PMC10086263/ /pubmed/37056336 http://dx.doi.org/10.3389/fonc.2023.1153353 Text en Copyright © 2023 Yuan, Xiao, Zhang, Mao, Wang and Wang 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 Oncology
Yuan, Wei
Xiao, Jun-hao
Zhang, Jian-song
Mao, Ben-liang
Wang, Peng-zhen
Wang, Bai-lin
Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title_full Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title_fullStr Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title_full_unstemmed Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title_short Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
title_sort identification of a cuproptosis and copper metabolism gene–related lncrnas prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086263/
https://www.ncbi.nlm.nih.gov/pubmed/37056336
http://dx.doi.org/10.3389/fonc.2023.1153353
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