Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, China.
Department of Neurology, Minzu Hospital of Guangxi Medical University, Nanning, 530001, China.
Mol Diagn Ther. 2024 Mar;28(2):225-235. doi: 10.1007/s40291-024-00694-1. Epub 2024 Feb 11.
The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection.
IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples.
Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of "limma" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83.
High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.
基因对颅内动脉瘤（IA）发病机制的影响尚待阐明，尚未建立可靠的用于诊断 IA 的血液生物标志物。本研究旨在通过分析 IA 数据集、进行血管平滑肌细胞（VSMC）实验和进行血液检测，鉴定与 IA 发病机制相关的基因，并探讨其诊断价值。
收集 IA 数据集并分析差异表达基因。在外部数据集中验证选定的基因。在 VSMC 中诱导自噬，并确定选定基因的作用。使用 IA 血浆样本的曲线下面积（AUC）分析探讨选定基因对 IA 的诊断价值。
使用“limma”包的经验贝叶斯方法分析 61 个样本（32 个对照和 29 个 IA 组织）发现 ADORA3 的表达与正常组织相比显著增加；这通过两个外部数据集进一步验证。此外，VSMC 中的自噬诱导导致 ADORA3 的上调。相反，沉默 ADORA3 抑制 VSMC 增殖和自噬。此外，对 IA 血液样本数据集和临床血浆样本的分析表明，IA 患者的 ADORA3 表达高于正常受试者。当分析临床样本时，血液 ADORA3 表达对 IA 的诊断价值中等（AUC：0.756）。将 ADORA3 与 IL2RB 或 CCR7 结合使用可进一步提高对 IA 的诊断能力，AUC 值超过 0.83。
ADORA3 的高表达与 IA 的发病机制有关，可能通过促进 VSMC 自噬。此外，血液 ADORA3 水平有可能作为 IA 的辅助诊断生物标志物。
