Abstract
Glioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan–Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.
Highlights
Glioblastoma (GBM), originating from astrocytes or oligodendrocytes precursor cells, is the most common and aggressive primary brain malignancy in adults and accounts for about 80% of malignant gliomas[1]
Liu et al found that the expression of Long non-coding RNAs (lncRNAs) SOX2OT was significantly up-regulated in temozolomide-resistant cells and samples from GBMrelapsed patients; and upregulation of SOX2OT was closely associated with poor prognosis of GBM patients
We analyzed the correlation of lncRNA and the 78 epithelial-mesenchymal transition (EMT)-related genes through Spearman correlation analysis and identified 301 lncRNAs which were significantly associated with EMT in GBM
Summary
Glioblastoma (GBM), originating from astrocytes or oligodendrocytes precursor cells, is the most common and aggressive primary brain malignancy in adults and accounts for about 80% of malignant gliomas[1]. Liu et al found that the expression of lncRNA SOX2OT was significantly up-regulated in temozolomide-resistant cells and samples from GBMrelapsed patients; and upregulation of SOX2OT was closely associated with poor prognosis of GBM patients. LncRNA SOX2OT upregulates SOX2 expression and activates Wnt5α/β-catenin signaling pathway, thereby facilitating cell proliferation and temozolomide resistance. These results suggested lncRNA SOX2OT could be used as a prognostic biomarker and a target of temozolomide resistance therapy for GBM p atients[11]. We explored the underlying mechanisms of the prognostic signature and found it was significantly correlated with multiple EMT and metastasis-related pathways, and immune activities of GBM
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