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A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding...

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Autores principales: Li, Guanghao, Liu, Yongheng, Zhang, Yanting, Xu, Yao, Zhang, Jin, Wei, Xianfu, Zhang, Zhongmin, Zhang, Chao, Feng, Jinyan, Li, Qiang, Wang, Guowen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304774/
https://www.ncbi.nlm.nih.gov/pubmed/35874689
http://dx.doi.org/10.3389/fimmu.2022.929089
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author Li, Guanghao
Liu, Yongheng
Zhang, Yanting
Xu, Yao
Zhang, Jin
Wei, Xianfu
Zhang, Zhongmin
Zhang, Chao
Feng, Jinyan
Li, Qiang
Wang, Guowen
author_facet Li, Guanghao
Liu, Yongheng
Zhang, Yanting
Xu, Yao
Zhang, Jin
Wei, Xianfu
Zhang, Zhongmin
Zhang, Chao
Feng, Jinyan
Li, Qiang
Wang, Guowen
author_sort Li, Guanghao
collection PubMed
description Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding RNAs (lncRNAs) can drive HCC initiation and progression. However, the prognostic value of ferroptosis-related lncRNAs in patients with HCC has not been explored comprehensively. Gene set variation analysis (GSVA) based on gene set and RNA-seq profiles obtained from public databases indicated that ferroptosis is suppressed in HCC patients. Ferroptosis-related differentially expressed lncRNAs were screened by Pearson’s test. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to establish a novel five ferroptosis-related lncRNA signature in the training cohort with 60% patients, which was further verified in the testing cohort with 40% patients. Dimensionality reduction analysis, Kaplan–Meier curve, receiver operating characteristic (ROC) curve, independent prognostic analysis, and stratification analysis confirmed that our signature had a high clinical application value in predicting the overall survival of HCC patients. Compared to the clinicopathological factors and the other four published HCC prognostic signatures, the current risk model had a better predictive value. The comparison results of functional enrichment, tumor immune microenvironment, genomic heterogeneity, and drug sensitivity between the high- and low-risk groups showed that the risk score is associated with extensive genomic alterations, immunosuppressive tumor microenvironment, and clinical treatment response. Finally, cell experiments showed that silencing LNCSRLR expression inhibited the growth, proliferation, migration, and invasion of the HCC cell line. Thus, the model can function as an efficient indicator for predicting clinical prognosis and treatment of anticancer drugs in HCC patients.
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spelling pubmed-93047742022-07-23 A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma Li, Guanghao Liu, Yongheng Zhang, Yanting Xu, Yao Zhang, Jin Wei, Xianfu Zhang, Zhongmin Zhang, Chao Feng, Jinyan Li, Qiang Wang, Guowen Front Immunol Immunology Hepatocellular carcinoma (HCC) with high heterogeneity is a common malignancy worldwide, but effective treatments are limited. Ferroptosis plays a critical role in tumors as a novel iron-dependent and reactive oxygen species-reliant type of cell death. Several studies have shown that long non-coding RNAs (lncRNAs) can drive HCC initiation and progression. However, the prognostic value of ferroptosis-related lncRNAs in patients with HCC has not been explored comprehensively. Gene set variation analysis (GSVA) based on gene set and RNA-seq profiles obtained from public databases indicated that ferroptosis is suppressed in HCC patients. Ferroptosis-related differentially expressed lncRNAs were screened by Pearson’s test. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were performed to establish a novel five ferroptosis-related lncRNA signature in the training cohort with 60% patients, which was further verified in the testing cohort with 40% patients. Dimensionality reduction analysis, Kaplan–Meier curve, receiver operating characteristic (ROC) curve, independent prognostic analysis, and stratification analysis confirmed that our signature had a high clinical application value in predicting the overall survival of HCC patients. Compared to the clinicopathological factors and the other four published HCC prognostic signatures, the current risk model had a better predictive value. The comparison results of functional enrichment, tumor immune microenvironment, genomic heterogeneity, and drug sensitivity between the high- and low-risk groups showed that the risk score is associated with extensive genomic alterations, immunosuppressive tumor microenvironment, and clinical treatment response. Finally, cell experiments showed that silencing LNCSRLR expression inhibited the growth, proliferation, migration, and invasion of the HCC cell line. Thus, the model can function as an efficient indicator for predicting clinical prognosis and treatment of anticancer drugs in HCC patients. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9304774/ /pubmed/35874689 http://dx.doi.org/10.3389/fimmu.2022.929089 Text en Copyright © 2022 Li, Liu, Zhang, Xu, Zhang, Wei, Zhang, Zhang, Feng, Li 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 Immunology
Li, Guanghao
Liu, Yongheng
Zhang, Yanting
Xu, Yao
Zhang, Jin
Wei, Xianfu
Zhang, Zhongmin
Zhang, Chao
Feng, Jinyan
Li, Qiang
Wang, Guowen
A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title_full A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title_fullStr A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title_full_unstemmed A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title_short A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma
title_sort novel ferroptosis-related long non-coding rna prognostic signature correlates with genomic heterogeneity, immunosuppressive phenotype, and drug sensitivity in hepatocellular carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304774/
https://www.ncbi.nlm.nih.gov/pubmed/35874689
http://dx.doi.org/10.3389/fimmu.2022.929089
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