Mining TCGA Database to Construct a RNA Binding Proteins-Related Prognostic Model for GBM

Abstract Background: Glioblastoma(GBM) is a common primary malignant brain tumor with poor prognosis, and currently effective therapeutic strategies are still limited. RNA binding proteins(RBPs) dysregulation has been reported in various cancers and is closely related to tumor initiation and progression. However, little is known about the role of RBPs in GBM.Methods: We downloaded RNA-seq transcriptome from TCGA database and differently expressed RBPs were screened between tumor and normal tissues. Then we performed functional enrichment analysis of these RBPs and based on univariate and multivariate cox regression analysis, hub RBPs were identified. Furthermore, we constructed a risk model based on hub RBPs and divided patients into high- and low-risk groups based on the median risk score. To validate the model, CGGA database were conducted as a training set and then both survival analysis and ROC curve were conducted. We also developed a nomogram based on five RBPs, which made more convenient to observe each patient’s prognosis and validated the connection between patients survival and each hub RBP . Finally, we used GEPIA website to further explore the value of these hub RBPs. Results: A total 309 differently expressed RBPs were identified, including 145 downregulated and 164 upregulated RBPs. and the result indicated that they were mainly enriched in mRNA processing, RNA splicing, RNA catabolic process, RNA transport, spliceosome, ribosome and mRNA surveillance pathway. Five hub RBPs were identified and we observed that patients with high risk score were related to poor overall survival and the AUC of ROC curve was 0.752 in TCGA. The result was subsequently proved by CGGA, showing the good prediction function of the model. Then GEPIA website suggested that MRPL41, MRPL36 and FBXO17 were closely associate with OS in GBM. Conclusion: Our result may provide novel insights into pathogenesis of GBM and development of new therapeutic targets. However, further experiments in vitro and in vivo will be warranted.