Identification of a 6-RBP gene signature for a comprehensive analysis of glioma and ischemic stroke: Cognitive impairment and aging-related hypoxic stress

Abstract

There is mounting evidence that ischemic cerebral infarction contributes to vascular cognitive impairment and dementia in elderly. Ischemic stroke and glioma are two majorly fatal diseases worldwide, which promote each other's development based on some common underlying mechanisms. As a post-transcriptional regulatory protein, RNA-binding protein is important in the development of a tumor and ischemic stroke (IS). The purpose of this study was to search for a group of RNA-binding protein (RBP) gene markers related to the prognosis of glioma and the occurrence of IS, and elucidate their underlying mechanisms in glioma and IS. First, a 6-RBP (POLR2F, DYNC1H1, SMAD9, TRIM21, BRCA1, and ERI1) gene signature (RBPS) showing an independent overall survival prognostic prediction was identified using the transcriptome data from TCGA-glioma cohort (n = 677); following which, it was independently verified in the CGGA-glioma cohort (n = 970). A nomogram, including RBPS, 1p19q codeletion, radiotherapy, chemotherapy, grade, and age, was established to predict the overall survival of patients with glioma, convenient for further clinical transformation. In addition, an automatic machine learning classification model based on radiomics features from MRI was developed to stratify according to the RBPS risk. The RBPS was associated with immunosuppression, energy metabolism, and tumor growth of gliomas. Subsequently, the six RBP genes from blood samples showed good classification performance for IS diagnosis (AUC = 0.95, 95% CI: 0.902–0.997). The RBPS was associated with hypoxic responses, angiogenesis, and increased coagulation in IS. Upregulation of SMAD9 was associated with dementia, while downregulation of POLR2F was associated with aging-related hypoxic stress. Irf5/Trim21 in microglia and Taf7/Trim21 in pericytes from the mouse cerebral cortex were identified as RBPS-related molecules in each cell type under hypoxic conditions. The RBPS is expected to serve as a novel biomarker for studying the common mechanisms underlying glioma and IS.