Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs

Long non-coding RNAs (lncRNAs) as important regulators of gene expression also have critical functions in immune regulation. This study identified lncRNA modulators of immune-related pathways as biomarkers for hepatocellular carcinoma (HCC). The profile of lncRNA regulation in immune pathways in HCC...

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Autores principales:	Hongsheng Lin, Yangyi Xie, Yinzhi Kong, Li Yang, Mingfen Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	long non-coding RNA (lncRNA) immune molecular subtypes hepatocellular carcinoma bioinformatics Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cbdc5476338449488d2e082560518d44
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spelling	oai:doaj.org-article:cbdc5476338449488d2e082560518d442021-11-30T12:51:32ZIdentification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs2296-889X10.3389/fmolb.2021.625858https://doaj.org/article/cbdc5476338449488d2e082560518d442021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.625858/fullhttps://doaj.org/toc/2296-889XLong non-coding RNAs (lncRNAs) as important regulators of gene expression also have critical functions in immune regulation. This study identified lncRNA modulators of immune-related pathways as biomarkers for hepatocellular carcinoma (HCC). The profile of lncRNA regulation in immune pathways in HCC was comprehensively mapped. To determine lncRNAs with immunomodulatory functions specific to HCC, the enrichment of lncRNAs in a collection of 17 immune functions was calculated applying gene set enrichment analysis (GSEA). Unsupervised clustering of samples were performed in the R package ConsensusClusterPlus to analyze subtype survival and immunological characteristics. The enrichment of 3,134 lncRNA–immune pathway pairs in both diseased and normal samples showed a total of 1,984 immunoregulatory functional lncRNAs specific to HCC only. In addition, 18 immune-related lncRNAs were disordered in HCC and were significantly associated with immune cell infiltration. Functional enrichment analysis indicated that the 18 dysregulated immune lncRNAs were enriched in cytokines, cytokine receptors, TGFb family members, TNF family members, and TNF family member receptor pathways. Two molecular subtypes of hepatocellular carcinoma were identified based on 18 dysregulated immune lncRNAs. Immunological profiling showed that subtype 1 samples with higher levels of cytokine response had a better survival, but subtype 2 samples with higher levels of tumor proliferation had poorer survival. This study identified 18 HCC-specific dysregulated immune lncRNAs and two HCC molecular subtypes with significant prognostic differences and immune characteristics. The current findings help understand the function of lncRNAs and promote the identification of immunotherapy targets.Hongsheng LinHongsheng LinHongsheng LinHongsheng LinYangyi XieYangyi XieYinzhi KongYinzhi KongLi YangLi YangMingfen LiMingfen LiFrontiers Media S.A.articlelong non-coding RNA (lncRNA)immunemolecular subtypeshepatocellular carcinomabioinformaticsBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	long non-coding RNA (lncRNA) immune molecular subtypes hepatocellular carcinoma bioinformatics Biology (General) QH301-705.5
spellingShingle	long non-coding RNA (lncRNA) immune molecular subtypes hepatocellular carcinoma bioinformatics Biology (General) QH301-705.5 Hongsheng Lin Hongsheng Lin Hongsheng Lin Hongsheng Lin Yangyi Xie Yangyi Xie Yinzhi Kong Yinzhi Kong Li Yang Li Yang Mingfen Li Mingfen Li Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
description	Long non-coding RNAs (lncRNAs) as important regulators of gene expression also have critical functions in immune regulation. This study identified lncRNA modulators of immune-related pathways as biomarkers for hepatocellular carcinoma (HCC). The profile of lncRNA regulation in immune pathways in HCC was comprehensively mapped. To determine lncRNAs with immunomodulatory functions specific to HCC, the enrichment of lncRNAs in a collection of 17 immune functions was calculated applying gene set enrichment analysis (GSEA). Unsupervised clustering of samples were performed in the R package ConsensusClusterPlus to analyze subtype survival and immunological characteristics. The enrichment of 3,134 lncRNA–immune pathway pairs in both diseased and normal samples showed a total of 1,984 immunoregulatory functional lncRNAs specific to HCC only. In addition, 18 immune-related lncRNAs were disordered in HCC and were significantly associated with immune cell infiltration. Functional enrichment analysis indicated that the 18 dysregulated immune lncRNAs were enriched in cytokines, cytokine receptors, TGFb family members, TNF family members, and TNF family member receptor pathways. Two molecular subtypes of hepatocellular carcinoma were identified based on 18 dysregulated immune lncRNAs. Immunological profiling showed that subtype 1 samples with higher levels of cytokine response had a better survival, but subtype 2 samples with higher levels of tumor proliferation had poorer survival. This study identified 18 HCC-specific dysregulated immune lncRNAs and two HCC molecular subtypes with significant prognostic differences and immune characteristics. The current findings help understand the function of lncRNAs and promote the identification of immunotherapy targets.
format	article
author	Hongsheng Lin Hongsheng Lin Hongsheng Lin Hongsheng Lin Yangyi Xie Yangyi Xie Yinzhi Kong Yinzhi Kong Li Yang Li Yang Mingfen Li Mingfen Li
author_facet	Hongsheng Lin Hongsheng Lin Hongsheng Lin Hongsheng Lin Yangyi Xie Yangyi Xie Yinzhi Kong Yinzhi Kong Li Yang Li Yang Mingfen Li Mingfen Li
author_sort	Hongsheng Lin
title	Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
title_short	Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
title_full	Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
title_fullStr	Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
title_full_unstemmed	Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs
title_sort	identification of two molecular subtypes of hepatocellular carcinoma based on dysregulated immune lncrnas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cbdc5476338449488d2e082560518d44
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Identification of Two Molecular Subtypes of Hepatocellular Carcinoma Based on Dysregulated Immune LncRNAs

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