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.

Association between multimorbidity and memory-related diseases among middle-aged and older adults: Evidence from the China Health and Retirement Longitudinal Study

“…There were some relevant studies in favor of this relationship, and there would be some mechanisms involved (32). A study reported that stroke was associated with cognitive impairment and dementia in older adults, and the six RNA-binding protein (RBP) genes (POLR2F, DYNC1H1, SMAD9, TRIM21, BRCA1, and ERI1) might participate in the process by mediating the hypoxic responses and angiogenesis (33). Regarding cardiovascular diseases and memory function, studies jointly found that better cardiovascular health is associated with lower memory decline and risk of cognitive impairment (34,35).…”

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma

“…Bioinformatic tools have become increasingly popular with the rapid development of high-throughput technology for assessing prognostic markers and studying mechanisms ( Wei et al, 2019 ; Shi et al, 2021 ; Luo et al, 2022a ; Luo et al, 2022b ; Chen et al, 2022 ; Lin et al, 2022 ; Mei et al, 2022 ; Xuan et al, 2022 ; Zhao and Jiang, 2022 ). In melanoma, lung cancer, and renal clear cell carcinoma, cuproptosis-related genes have been studied.…”

Predictors of cognitive impairment in patients undergoing ileostomy for colorectal cancer: a retrospective analysis

“…Predictive models can also assist physicians in implementing precision medicine, thereby formulating more personalized and efficacious treatment plans ( Pencina & Peterson, 2016 ; Obermeyer & Emanuel, 2016 ; Kang et al, 2020 ; Wu et al, 2021 ; Lin et al, 2022 ; Chen et al, 2022a ). These models can enhance research efficiency, accelerate the development of novel pharmaceuticals, and optimize therapeutic strategies, ultimately making significant contributions to the improvement of human health.…”