Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma
Ferroptosis is an iron-dependent cell death process that plays important regulatory roles in the occurrence and development of cancers, including hepatocellular carcinoma (HCC). Moreover, the molecular events surrounding aberrantly expressed long non-coding RNAs (lncRNAs) that drive HCC initiation a...
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Format: | Article |
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Frontiers Media S.A.
2021-09-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.719175/full |
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doaj-75359dd43ef541679c59364f1c87f24a |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhijie Xu Bi Peng Qiuju Liang Qiuju Liang Xi Chen Xi Chen Yuan Cai Shuangshuang Zeng Shuangshuang Zeng Kewa Gao Xiang Wang Xiang Wang Qiaoli Yi Qiaoli Yi Zhicheng Gong Zhicheng Gong Yuanliang Yan Yuanliang Yan |
spellingShingle |
Zhijie Xu Bi Peng Qiuju Liang Qiuju Liang Xi Chen Xi Chen Yuan Cai Shuangshuang Zeng Shuangshuang Zeng Kewa Gao Xiang Wang Xiang Wang Qiaoli Yi Qiaoli Yi Zhicheng Gong Zhicheng Gong Yuanliang Yan Yuanliang Yan Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma Frontiers in Immunology ferroptosis immune cell infiltrate lncRNA hepatocellular carcinoma survival analysis |
author_facet |
Zhijie Xu Bi Peng Qiuju Liang Qiuju Liang Xi Chen Xi Chen Yuan Cai Shuangshuang Zeng Shuangshuang Zeng Kewa Gao Xiang Wang Xiang Wang Qiaoli Yi Qiaoli Yi Zhicheng Gong Zhicheng Gong Yuanliang Yan Yuanliang Yan |
author_sort |
Zhijie Xu |
title |
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma |
title_short |
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma |
title_full |
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma |
title_fullStr |
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma |
title_full_unstemmed |
Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma |
title_sort |
construction of a ferroptosis-related nine-lncrna signature for predicting prognosis and immune response in hepatocellular carcinoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-09-01 |
description |
Ferroptosis is an iron-dependent cell death process that plays important regulatory roles in the occurrence and development of cancers, including hepatocellular carcinoma (HCC). Moreover, the molecular events surrounding aberrantly expressed long non-coding RNAs (lncRNAs) that drive HCC initiation and progression have attracted increasing attention. However, research on ferroptosis-related lncRNA prognostic signature in patients with HCC is still lacking. In this study, the association between differentially expressed lncRNAs and ferroptosis-related genes, in 374 HCC and 50 normal hepatic samples obtained from The Cancer Genome Atlas (TCGA), was evaluated using Pearson’s test, thereby identifying 24 ferroptosis-related differentially expressed lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model were used to construct and validate a prognostic risk score model from both TCGA training dataset and GEO testing dataset (GSE40144). A nine-lncRNA-based signature (CTD-2033A16.3, CTD-2116N20.1, CTD-2510F5.4, DDX11-AS1, LINC00942, LINC01224, LINC01231, LINC01508, and ZFPM2-AS1) was identified as the ferroptosis-related prognostic model for HCC, independent of multiple clinicopathological parameters. In addition, the HCC patients were divided into high-risk and low-risk groups according to the nine-lncRNA prognostic signature. The gene set enrichment analysis enrichment analysis revealed that the lncRNA-based signature might regulate the HCC immune microenvironment by interfering with tumor necrosis factor α/nuclear factor kappa-B, interleukin 2/signal transducers and activators of transcription 5, and cytokine/cytokine receptor signaling pathways. The infiltrating immune cell subtypes, such as resting memory CD4(+) T cells, follicular helper T cells, regulatory T cells, and M0 macrophages, were all significantly different between the high-risk group and the low-risk group as indicated in Spearman’s correlation analysis. Moreover, a substantial increase in the expression of B7H3 immune checkpoint molecule was found in the high-risk group. Our findings provided a promising insight into ferroptosis-related lncRNAs in HCC and a personalized prediction tool for prognosis and immune responses in patients. |
topic |
ferroptosis immune cell infiltrate lncRNA hepatocellular carcinoma survival analysis |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.719175/full |
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doaj-75359dd43ef541679c59364f1c87f24a2021-09-17T04:37:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.719175719175Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular CarcinomaZhijie Xu0Bi Peng1Qiuju Liang2Qiuju Liang3Xi Chen4Xi Chen5Yuan Cai6Shuangshuang Zeng7Shuangshuang Zeng8Kewa Gao9Xiang Wang10Xiang Wang11Qiaoli Yi12Qiaoli Yi13Zhicheng Gong14Zhicheng Gong15Yuanliang Yan16Yuanliang Yan17Department of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaFerroptosis is an iron-dependent cell death process that plays important regulatory roles in the occurrence and development of cancers, including hepatocellular carcinoma (HCC). Moreover, the molecular events surrounding aberrantly expressed long non-coding RNAs (lncRNAs) that drive HCC initiation and progression have attracted increasing attention. However, research on ferroptosis-related lncRNA prognostic signature in patients with HCC is still lacking. In this study, the association between differentially expressed lncRNAs and ferroptosis-related genes, in 374 HCC and 50 normal hepatic samples obtained from The Cancer Genome Atlas (TCGA), was evaluated using Pearson’s test, thereby identifying 24 ferroptosis-related differentially expressed lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression model were used to construct and validate a prognostic risk score model from both TCGA training dataset and GEO testing dataset (GSE40144). A nine-lncRNA-based signature (CTD-2033A16.3, CTD-2116N20.1, CTD-2510F5.4, DDX11-AS1, LINC00942, LINC01224, LINC01231, LINC01508, and ZFPM2-AS1) was identified as the ferroptosis-related prognostic model for HCC, independent of multiple clinicopathological parameters. In addition, the HCC patients were divided into high-risk and low-risk groups according to the nine-lncRNA prognostic signature. The gene set enrichment analysis enrichment analysis revealed that the lncRNA-based signature might regulate the HCC immune microenvironment by interfering with tumor necrosis factor α/nuclear factor kappa-B, interleukin 2/signal transducers and activators of transcription 5, and cytokine/cytokine receptor signaling pathways. The infiltrating immune cell subtypes, such as resting memory CD4(+) T cells, follicular helper T cells, regulatory T cells, and M0 macrophages, were all significantly different between the high-risk group and the low-risk group as indicated in Spearman’s correlation analysis. Moreover, a substantial increase in the expression of B7H3 immune checkpoint molecule was found in the high-risk group. Our findings provided a promising insight into ferroptosis-related lncRNAs in HCC and a personalized prediction tool for prognosis and immune responses in patients.https://www.frontiersin.org/articles/10.3389/fimmu.2021.719175/fullferroptosisimmune cell infiltratelncRNAhepatocellular carcinomasurvival analysis |