Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma

BackgroundGlioblastoma multiforme (GBM) is extensively genetically and transcriptionally heterogeneous, which poses challenges for classification and management. Long noncoding RNAs (lncRNAs) play a critical role in the development and progression of GBM, especially in tumor-associated immune proces...

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Autores principales:	Wanli Yu, Yanan Ma, Wenbin Hou, Fang Wang, Wan Cheng, Feng Qiu, Pengfei Wu, Guohua Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glioblastoma immune-related lncRNAs biomarker prognostic signature immune infiltration Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/fed755558c4c40a7b80e9e20215d2059
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spelling	oai:doaj.org-article:fed755558c4c40a7b80e9e20215d20592021-12-01T03:03:07ZIdentification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma1664-322410.3389/fimmu.2021.706936https://doaj.org/article/fed755558c4c40a7b80e9e20215d20592021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.706936/fullhttps://doaj.org/toc/1664-3224BackgroundGlioblastoma multiforme (GBM) is extensively genetically and transcriptionally heterogeneous, which poses challenges for classification and management. Long noncoding RNAs (lncRNAs) play a critical role in the development and progression of GBM, especially in tumor-associated immune processes. Therefore, it is necessary to develop an immune-related lncRNAs (irlncRNAs) signature.MethodsUnivariate and multivariate Cox regression analyses were utilized to construct a prognostic model. GBM-specific CeRNA and PPI network was constructed to predict lncRNAs targets and evaluate the interactions of immune mRNAs translated proteins. GO and KEGG pathway analyses were used to show the biological functions and pathways of CeRNA network-related immunity genes. Consensus Cluster Plus analysis was used for GBM gene clustering. Then, we evaluated GBM subtype-specific prognostic values, clinical characteristics, genes and pathways, immune infiltration access single cell RNA-seq data, and chemotherapeutics efficacy. The hub genes were finally validated.ResultsA total of 17 prognostically related irlncRNAs were screened to build a prognostic model signature based on six key irlncRNAs. Based on GBM-specific CeRNAs and enrichment analysis, PLAU was predicted as a target of lncRNA-H19 and mainly enriched in the malignant related pathways. GBM subtype-A displayed the most favorable prognosis, high proportion of genes (IDH1, ATRX, and EGFR) mutation, chemoradiotherapy, and low risk and was characterized by low expression of four high-risk lncRNAs (H19, HOTAIRM1, AGAP2-AS1, and AC002456.1) and one mRNA KRT8. GSs with poor survival were mainly infiltrated by mesenchymal stem cells (MSCs) and astrocyte, and were more sensitive to gefitinib and roscovitine. Among GSs, three hub genes KRT8, NGFR, and TCEA3, were screened and validated to potentially play feasible oncogenic roles in GBM.ConclusionConstruction of lncRNAs risk model and identification of GBM subtypes based on 17 irlncRNAs, which suggesting that irlncRNAs had the promising potential for clinical immunotherapy of GBM.Wanli YuWanli YuYanan MaWenbin HouFang WangWan ChengFeng QiuPengfei WuPengfei WuPengfei WuPengfei WuGuohua ZhangFrontiers Media S.A.articleglioblastomaimmune-related lncRNAsbiomarkerprognostic signatureimmune infiltrationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioblastoma immune-related lncRNAs biomarker prognostic signature immune infiltration Immunologic diseases. Allergy RC581-607
spellingShingle	glioblastoma immune-related lncRNAs biomarker prognostic signature immune infiltration Immunologic diseases. Allergy RC581-607 Wanli Yu Wanli Yu Yanan Ma Wenbin Hou Fang Wang Wan Cheng Feng Qiu Pengfei Wu Pengfei Wu Pengfei Wu Pengfei Wu Guohua Zhang Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
description	BackgroundGlioblastoma multiforme (GBM) is extensively genetically and transcriptionally heterogeneous, which poses challenges for classification and management. Long noncoding RNAs (lncRNAs) play a critical role in the development and progression of GBM, especially in tumor-associated immune processes. Therefore, it is necessary to develop an immune-related lncRNAs (irlncRNAs) signature.MethodsUnivariate and multivariate Cox regression analyses were utilized to construct a prognostic model. GBM-specific CeRNA and PPI network was constructed to predict lncRNAs targets and evaluate the interactions of immune mRNAs translated proteins. GO and KEGG pathway analyses were used to show the biological functions and pathways of CeRNA network-related immunity genes. Consensus Cluster Plus analysis was used for GBM gene clustering. Then, we evaluated GBM subtype-specific prognostic values, clinical characteristics, genes and pathways, immune infiltration access single cell RNA-seq data, and chemotherapeutics efficacy. The hub genes were finally validated.ResultsA total of 17 prognostically related irlncRNAs were screened to build a prognostic model signature based on six key irlncRNAs. Based on GBM-specific CeRNAs and enrichment analysis, PLAU was predicted as a target of lncRNA-H19 and mainly enriched in the malignant related pathways. GBM subtype-A displayed the most favorable prognosis, high proportion of genes (IDH1, ATRX, and EGFR) mutation, chemoradiotherapy, and low risk and was characterized by low expression of four high-risk lncRNAs (H19, HOTAIRM1, AGAP2-AS1, and AC002456.1) and one mRNA KRT8. GSs with poor survival were mainly infiltrated by mesenchymal stem cells (MSCs) and astrocyte, and were more sensitive to gefitinib and roscovitine. Among GSs, three hub genes KRT8, NGFR, and TCEA3, were screened and validated to potentially play feasible oncogenic roles in GBM.ConclusionConstruction of lncRNAs risk model and identification of GBM subtypes based on 17 irlncRNAs, which suggesting that irlncRNAs had the promising potential for clinical immunotherapy of GBM.
format	article
author	Wanli Yu Wanli Yu Yanan Ma Wenbin Hou Fang Wang Wan Cheng Feng Qiu Pengfei Wu Pengfei Wu Pengfei Wu Pengfei Wu Guohua Zhang
author_facet	Wanli Yu Wanli Yu Yanan Ma Wenbin Hou Fang Wang Wan Cheng Feng Qiu Pengfei Wu Pengfei Wu Pengfei Wu Pengfei Wu Guohua Zhang
author_sort	Wanli Yu
title	Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
title_short	Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
title_full	Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
title_fullStr	Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
title_full_unstemmed	Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma
title_sort	identification of immune-related lncrna prognostic signature and molecular subtypes for glioblastoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fed755558c4c40a7b80e9e20215d2059
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Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma

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