Identification and Validation of an Immune-Associated RNA-Binding Proteins Signature to Predict Clinical Outcomes and Therapeutic Responses in Glioma Patients

SIMPLE SUMMARY: Both of tumor-infiltrating immune cells and the RNA-binding proteins (RBPs) that are able to mediate immune infiltration contribute to the prognosis of patients with glioma. However, immune-associated RBPs in glioma remain unexplored. In this study, we developed a method to identify RBPs associated with immune infiltration in glioma and 216 RBPs were defined as immune-associated RBPs. Among them, eight RBPs were selected to construct a risk signature that proved to be a novel and independent prognostic factor. Higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints. Additionally, analyses of pathway enrichment, somatic mutation, copy number variations, and immuno-/chemotherapeutic response prediction were performed to evaluate the differences between high- and low-risk groups. Generally, we demonstrated an eight immune-associated RBPs prognostic signature that was valuable in predicting the survival of glioma patients and directing immunotherapy and chemotherapy. ABSTRACT: The prognosis of patients with glioma is largely related to both the tumor-infiltrating immune cells and the expression of RNA-binding proteins (RBPs) that are able to regulate various pro-inflammatory and oncogenic mediators. However, immune-associated RBPs in glioma remain unexplored. In this study, we captured patient data from The Cancer Genome Atlas (TCGA) and divided them into two immune subtype groups according to the difference in infiltration of immune cells. After differential expression and co-expression analysis, we identified 216 RBPs defined as immune-associated RBPs. After narrowing down processes, eight RBPs were selected out to construct a risk signature that proven to be a novel and independent prognostic factor. The patients were divided into high- and low-risk groups on the basis of risk score. Higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints such as PD1 and CTLA4. In addition, analyses of pathway enrichment, somatic mutation, copy number variations and immuno-/chemotherapeutic response prediction were performed in high- and low-risk groups and compared with each other. For the first time, we demonstrated a novel signature composed of eight immune-associated RBPs that was valuable in predicting the survival of glioma patients and directing immunotherapy and chemotherapy.