Intracranial Aneurysms Induced by RUNX1 Through Regulation of NFKB1 in Patients With Hypertension-An Integrated Analysis Based on Multiple Datasets and Algorithms

Yang Li; Zhen Zhang; Donghua Liu

doi:10.3389/fneur.2022.877801

Intracranial Aneurysms Induced by RUNX1 Through Regulation of NFKB1 in Patients With Hypertension-An Integrated Analysis Based on Multiple Datasets and Algorithms

Front Neurol. 2022 May 17:13:877801. doi: 10.3389/fneur.2022.877801. eCollection 2022.

Authors

Yang Li¹, Zhen Zhang², Donghua Liu³

Affiliations

¹ Department of Neurosurgery, The First People's Hospital of Yinchuan, Yinchuan, China.
² Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
³ Department of Neurosurgery, The Second People's Hospital of Yinchuan, Yinchuan, China.

Abstract

Objective: The purpose of this study was to identify potential therapeutic targets by examining the hub genes contributing to progression of intracranial aneurysm (IA) in patients with hypertension.

Methods: The bulk RNA sequencing (RNA-seq) datasets of hypertension and IA were obtained from the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo) database. These data were then used to calculate disease-related differentially expressed genes (DEGs) at the individual level. An scRNA-seq dataset of patients with abdominal aortic aneurysms (AAA) was used to analyze monocyte/macrophage-related DEGs. On the basis of the DEG data related to monocytes and macrophages, a TF-genes network has been developed. Hub genes and core sub-networks have also been identified. Furthermore, the key genes have been validated in an external cohort.

Results: From combined monocyte and macrophage-derived DEGs from abdominal aortic aneurysms, five hub DEGs were detected, including IFI30, SERPINE1, HMOX1, IL24, and RUNX1. A total of 57 genes were found in the IA bulk RNA-seq dataset. A support vector machine-recursive feature elimination algorithm (SVM-RFE) was applied to further screen the seven genes (RPS4Y1, DDX3Y, RUNX1, CLEC10A, PLAC8, SLA, and LILRB3). RUNX1 was the hub gene that regulated NFKB1 in the monocyte/macrophage-related network. And RUNX1 is implicated in IA progression by regulating hematopoietic stem cell differentiation and abnormal platelet production, according to gene set enrichment analysis.

Conclusion: Among patients with hypertension, RUNX1 in monocytes and macrophages was associated with a higher risk of IA through its regulation of NFKB1.

Keywords: NFKB1; Runx1; hypertension; intracranial aneurysm (IA); monocytes/macrophages.