Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is the most frequent intracranial primary malignancy in adults
A total of 17 prognostically related irlncRNAs were screened to build a prognostic model signature based on six key irlncRNAs
Construction of Long noncoding RNAs (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
Summary
Glioblastoma multiforme (GBM) is the most frequent intracranial primary malignancy in adults. Recent studies have shown that lncRNAs can influence the tumor immune microenvironment (TIM) by regulating inflammation and participating in immune gene expression [5, 6]. LncRNA-Cox participates in inflammatory gene expression in macrophages via regulating chromatin complex remodeling [8]. Increasing studies reporting on the mechanism of irlncRNAs in multiple cancers [10], the ambiguous relationship between lncRNAs, and the tumor immune microenvironment have been gradually unveiled. The relationship between lncRNAs and tumor immune microenvironment is rarely studied in GBM. Glioblastoma 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. It is necessary to develop an immune-related lncRNAs (irlncRNAs) signature
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