Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Province, No. 299, Bianhe Zhong Lu District, Suzhou City, Hefei, 234000, China.
Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou, China.
BMC Genom Data. 2023 Apr 11;24(1):20. doi: 10.1186/s12863-023-01121-w.
Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA.
All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR.
In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results.
The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management.
颅内动脉瘤（IA）是一种常见的脑血管疾病。IA 的免疫机制更为复杂，目前尚不清楚。因此，有必要继续探索 IA 的免疫相关分子机制。
所有数据均从公共数据库下载。使用 Limma 包和 ssGSEA 算法分别识别差异表达的 mRNAs（DEmRNAs）和分析免疫细胞浸润。使用机器学习和 cytoscape-cytohubba 插件分别识别 IA 的关键免疫类型和多中心 DEmRNAs。通过 Spearman 相关性分析筛选出与关键免疫细胞相关的多中心 DEmRNAs 作为关键 DEmRNAs。基于关键 DEmRNAs 构建诊断模型、竞争性内源性 RNA（ceRNA）调控网络和转录因子调控网络。同时，根据 DGIdb 数据库筛选出与关键 DEmRNAs 相关的药物。通过实时 PCR 验证关键 DEmRNAs 的表达。
本研究鉴定出 7 个与关键差异免疫细胞浸润（CD56bright 自然杀伤细胞、未成熟 B 细胞和 1 型 T 辅助细胞）相关的关键 DEmRNAs（NRXN1、GRIA2、SLC1A2、SLC17A7、IL6、VEGFA 和 SYP）。功能富集分析表明，VEGFA 和 IL6 可能参与 PI3K-Akt 信号通路的调节。此外，还发现 IL6 富集在细胞因子-细胞因子受体相互作用信号通路中。在 ceRNA 调控网络中，发现了大量的 miRNAs 和 lncRNAs。在转录因子调控网络中，转录因子 SP1 与 VEGFA、SYP 和 IL6 相关。还预测了与关键 DEmRNAs 相关的药物，如 CARBOPLATIN、FENTANYL 和 CILOSTAZOL，可能有助于治疗 IA。此外，还发现基于关键 DEmRNAs 的 SVM 和 RF 模型可能分别是诊断 IA 和未破裂颅内动脉瘤（UIA）的潜在标志物。实时 PCR 验证的关键 DEmRNAs 的表达趋势与生物信息学分析结果一致。
本研究中鉴定的分子和途径为了解 IA 的免疫相关分子机制提供了理论基础。同时，药物预测和诊断模型的构建也可能有助于临床诊断和管理。
