Abstract
ObjectiveThe present study used the RNA sequencing (RNA-seq) dataset to identify prognostic snoRNAs and construct a prognostic signature of The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort, and comprehensive analysis of this signature.MethodsRNA-seq dataset of 488 patients from TCGA LGG cohort were included in this study. Comprehensive analysis including function enrichment, gene set enrichment analysis (GSEA), immune infiltration, cancer immune microenvironment, and connectivity map (CMap) were used to evaluate the snoRNAs prognostic signature.ResultsWe identified 21 LGG prognostic snoRNAs and constructed a novel eleven-snoRNA prognostic signature for LGG patients. Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor (adjusted P = 0.003, adjusted hazard ratio = 2.076, 95% confidence interval = 1.290–3.340). GSEA and functional enrichment analysis suggest that this signature may be involved in the following biological processes and signaling pathways: such as cell cycle, Wnt, mitogen-activated protein kinase, janus kinase/signal transducer and activator of tran-ions, T cell receptor, nuclear factor-kappa B signaling pathway. CMap analysis screened out ten targeted therapy drugs for this signature: 15-delta prostaglandin J2, MG-262, vorinostat, 5155877, puromycin, anisomycin, withaferin A, ciclopirox, chloropyrazine and megestrol. We also found that high- and low-risk score phenotypes of LGG patients have significant differences in immune infiltration and cancer immune microenvironment.ConclusionsThe present study identified a novel eleven-snoRNA prognostic signature of LGG and performed a integrative analysis of its molecular mechanisms and relationship with tumor immunity.
Highlights
Tumors derived from the neuroepithelium are collectively called gliomas and are the most common malignant primary intracranial tumor [1]
RNA sequencing (RNA-seq) dataset of 488 patients from The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort were included in this study
Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor
Summary
Tumors derived from the neuroepithelium are collectively called gliomas and are the most common malignant primary intracranial tumor [1]. Just like any other cancers, glioma is due to the interaction of innate genetic risk factors and environmental carcinogenic factors (e.g., radiation exposure). With the development of high-throughput sequencing technology, we have found that more and more genetic variants are connected with the occurrence, development and clinical outcome of cancers. TCGA is a database resource for whole-genome multi-omics sequencing of 33 human cancers based on high-throughput sequencing technology [3]. It can provide the whole genome multi-omics data set of glioma, so that we can further explore its genetic variation [4]
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