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

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.

Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer

“…The clinical data and transcriptome data were retrieved from the TCGA database, including 1,096 BRCA specimens and 112 normal specimens. We performed Spearman correlation analysis between the lncRNAs and NRGs, and 1,520 necroptosis-related lncRNAs (NRlncRNAs) were sorted out with the filter criteria of correlation coefficients >0.4 and p < 0.001 ( 21 , 22 , 31 , 32 ) ( Table S1 and Figure 2A ). Forty-six prognostic NRlncRNAs in BRCA were extracted by univariate analysis, of which the significant filtering condition was p < 0.05 ( Table S2 and Figures 2B, C ).…”

Prognostic Features of the Tumor Immune Microenvironment in Glioma and Their Clinical Applications: Analysis of Multiple Cohorts

“…Recently, a large scale of bioinformatics studies utilized public data resources to identify glioma prognostic signatures, including gene signatures ( 35 – 40 ), lncRNA signature ( 41 ), and gene-set signature ( 42 , 43 ). The summary of all of these prognostic studies and our study was displayed in Table S4 .…”

Keratin 8 Is an Inflammation-Induced and Prognosis-Related Marker for Pancreatic Adenocarcinoma

“…Second, the differences in KRT8 expression between PDAC and normal pancreas tissue were statistically significant (Figures 3(a) – 3(d) ). Recent studies revealed that the overexpression of KRT8 could be also found in glioblastoma [ 43 ]. Interestingly, Nordgård et al found that KRT8 was upregulated in the bone marrow aspirates from advanced PDAC patients, possibly caused by infiltrated PDAC cells, indicating the potential role of KRT8 in the formation of tumour microenvironment [ 44 ].…”