Abstract
BackgroundMolecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. Recent studies have highlighted that long non-coding RNAs (lncRNAs) are key mediators in cancer mesenchymal transition. However, the relationship between lncRNAs and PMT in glioma has not been systematically investigated.MethodsGene expression profiles from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, and Rembrandt with available clinical and genomic information were used for analyses. Bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), Cox analysis, and least absolute shrinkage and selection operator (LASSO) analysis were performed.ResultsAccording to PMT scores, we confirmed that PMT status was positively associated with risky behaviors and poor prognosis in glioma. The 149 PMT-related lncRNAs were identified by WGCNA analysis, among which 10 (LINC01057, TP73-AS1, AP000695.4, LINC01503, CRNDE, OSMR-AS1, SNHG18, AC145343.2, RP11-25K21.6, RP11-38L15.2) with significant prognostic value were further screened to construct a PMT-related lncRNA risk signature, which could divide cases into two groups with distinct prognoses. Multivariate Cox regression analyses indicated that the signature was an independent prognostic factor for high-grade glioma. High-risk cases were more likely to be classified as the mesenchymal subtype, which confers enhanced immunosuppressive status by recruiting macrophages, neutrophils, and regulatory T cells. Moreover, six lncRNAs of the signature could act as competing endogenous RNAs to promote PMT in glioblastoma.ConclusionsWe profiled PMT status in glioma and established a PMT-related 10-lncRNA signature for glioma that could independently predict glioma survival and trigger PMT, which enhanced immunosuppression.
Highlights
Molecular classification has laid the framework for exploring glioma biology and treatment strategies
Pro-neural to mesenchymal transition (PMT) scores were positively associated with the risky behaviors of gliomas To explore the general pattern of PMT status in glioma, we compared the distribution of PMT scores according to World Health Organization (WHO) grade, histology, and molecular subtype
We found that PMT scores were increased with increased risky progression of gliomas
Summary
Molecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. To explore more effective treatments, molecular subtypes related to GBM prognosis have been identified based on large genomic data. GBM was classified into four molecular subtypes: pro-neural (PN), neural (NL), classical (CL), and mesenchymal (MES) [3]. Transition among the subtypes often occurs during gliomagenesis, which induces biological heterogeneity, poor prognosis, and therapeutic resistance [4, 5]. Among the four molecular subtypes, glioma cells cultured in vitro are mostly classified into PN or MES and show distinct biological features [4]. Remnant gliomas after radiotherapy and/or chemotherapy can undergo pro-neural to mesenchymal transition (PMT), which is associated with treatment resistance [7]. Uncovering the mechanisms that underlie PMT is urgently needed to improve glioma treatments
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