Abstract

Objective: Increasing evidence emphasizes the clinical implications of RNA binding proteins (RBPs) in cancers. This study aimed to develop a RBP signature for predicting prognosis in glioma.Methods: Two glioma datasets as training (n = 693) and validation (n = 325) sets were retrieved from the CGGA database. In the training set, univariate Cox regression analysis was conducted to screen prognosis-related RBPs based on differentially expressed RBPs between WHO grade II and IV. A ten-RBP signature was then established. The predictive efficacy was evaluated by ROCs. The applicability was verified in the validation set. The pathways involving the risk scores were analyzed by ssGSEA. scRNA-seq was utilized for evaluating their expression in different glioma cell types. Moreover, their expression was externally validated between glioma and control samples.Results: Based on 39 prognosis-related RBPs, a ten RBP signature was constructed. High risk score distinctly indicated a poorer prognosis than low risk score. AUCs were separately 0.838 and 0.822 in the training and validation sets, suggesting its well performance for prognosis prediction. Following adjustment of other clinicopathological characteristics, the signature was an independent risk factor. Various cancer-related pathways were significantly activated in samples with high risk score. The scRNA-seq identified that risk RBPs were mainly expressed in glioma malignant cells. Their high expression was also found in glioma than control samples.Conclusion: This study developed a novel RBP signature for robustly predicting prognosis of glioma following multi-data set verification. These RBPs may affect the progression of glioma.

Highlights

  • Glioma is the most frequently diagnosed primary brain malignancy, accounting for 70% of all brain malignancies [1]

  • With the criteria of |log fold change (FC)| ≥ 0.58 and false discovery rate (FDR) > 0.5, 40 RNA binding proteins (RBPs) were abnormally expressed between glioma II and IV samples (Supplementary Table 1)

  • To further probe the biological functions of these prognosis-related RBPs, we carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis

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Summary

Introduction

Glioma is the most frequently diagnosed primary brain malignancy, accounting for 70% of all brain malignancies [1]. The incidence of lower grade gliomas (LGG) WHO grade II is relatively lower and patients with grade II exhibit better clinical outcomes and more sensitive to therapies [3]. The diagnosis of glioma primarily depends on histopathology, imaging as well as molecular diagnosis [4,5,6]. Because of complicacy and heterogeneity, traditionally diagnostic and therapeutic techniques exert side effects for the clinical outcomes of patients. To prolong the survival time of patients, it is of clinical importance for discovering novel accurate molecular biomarkers for prognosis prediction in glioma

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