Discovering Common Genetic Markers for Glioma and Ischemic Stroke

Published on September 1, 2022

Imagine glioma and ischemic stroke as two powerful superheroes with a special connection. Just like superheroes, these diseases have common mechanisms that drive their development. In this exciting study, scientists aimed to find RNA-binding protein (RBP) genes that could be used as markers to predict the prognosis of glioma and the occurrence of ischemic stroke. After careful analysis of transcriptome data, they identified a signature of 6 RBP genes that showed independent predictive power for overall survival in patients with glioma. The results were then validated in an independent glioma cohort. By incorporating these genes into a predictive model, researchers were able to create a handy nomogram that could help clinicians in making treatment decisions for glioma patients. Furthermore, using radiomics features from MRI scans, they developed a machine learning model to stratify patients based on their risk status determined by the RBP gene signature. The RBP genes were also found to be associated with immunosuppression, energy metabolism, and tumor growth in gliomas. Additionally, these genes showed promise in diagnosing ischemic stroke, with an impressive diagnostic performance. Upregulation of SMAD9 was linked to dementia, while downregulation of POLR2F was associated with aging-related hypoxic stress. The study also identified specific RBPS-related molecules in different cell types under hypoxic conditions. This groundbreaking research provides new insights into the shared molecular pathways between glioma and ischemic stroke, paving the way for potential biomarkers and future investigations.

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.

Read Full Article (External Site)

Leave a Reply

Your email address will not be published. Required fields are marked *

You may use these HTML tags and attributes:

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>