METHODS: Differential genes related to BNST were identified from the GEO database. Gene co-expression networks, protein-protein interaction networks, and LASSO regression were utilized to pinpoint key genes. The CIBERSORT algorithm assessed immune cell infiltration differences, and functional enrichment analyses explored BNST signaling pathways. Clinical samples helped establish PDX models, and in vitro cell lines to validate NRG1\'s role via the PI3K-Akt pathway.
RESULTS: Nine hundred eighty-two genes were upregulated, and 375 downregulated in BNST samples. WGCNA revealed the brown module with the most significant difference. Top hub genes included NRG1, which was also determined as a pivotal gene in disease characterization. Immune infiltration showed significant variances in neutrophils and M2 macrophages, with NRG1 playing a central role. Functional analyses confirmed NRG1\'s involvement in key pathways. Validation experiments using PDX models and cell lines further solidified NRG1\'s role in BNST.
CONCLUSIONS: NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.
方法:从GEO数据库中鉴定出与BNST相关的差异基因。基因共表达网络,蛋白质-蛋白质相互作用网络,和LASSO回归用于确定关键基因。TheCIBERSORT算法评估免疫细胞浸润差异,和功能富集分析探索了BNST信号通路。临床样本帮助建立PDX模型,和体外细胞系通过PI3K-Akt途径验证NRG1的作用。
结果:98个基因上调,在BNST样品中下调了375个。WGCNA显示棕色模块具有最显著的差异。顶级中心基因包括NRG1,它也被确定为疾病表征中的关键基因。免疫浸润显示中性粒细胞和M2巨噬细胞的显著差异,NRG1发挥核心作用。功能分析证实NRG1参与关键通路。使用PDX模型和细胞系的验证实验进一步巩固了NRG1在BNST中的作用。
结论:NRG1成为BNST的潜在诊断生物标志物,影响PI3K-Akt通路,塑造肿瘤免疫微环境。