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

Weiwei Lin; Qiangwei Wang; Yisheng Chen; Ning Wang; Qingbin Ni; Chunhua Qi; Qian Wang; Yongjian Zhu

doi:10.3389/fnagi.2022.951197

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

Front Aging Neurosci. 2022 Sep 1:14:951197. doi: 10.3389/fnagi.2022.951197. eCollection 2022.

Authors

Weiwei Lin^{1

2}, Qiangwei Wang^{1

2}, Yisheng Chen³, Ning Wang⁴, Qingbin Ni⁵, Chunhua Qi⁵, Qian Wang⁵, Yongjian Zhu^{1

2

6}

Affiliations

¹ Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases of Zhejiang, Hangzhou, China.
³ Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Postdoctoral Workstation, Department of Central Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China.
⁶ College of Mathematical Medicine, Zhejiang Normal University, Jinhua, China.

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.

Keywords: RNA binding protein (RBP); dementia; elderly; glioma; ischemic stroke.