Diagnostic potential of NRG1 in benign nerve sheath tumors and its influence on the PI3K-Akt signaling and tumor immunity

Abstract

Abstract Objective Benign nerve sheath tumors (BNSTs) present diagnostic challenges due to their heterogeneous nature. This study aimed to determine the significance of NRG1 as a novel diagnostic biomarker in BNST, emphasizing its involvement in the PI3K-Akt pathway and tumor immune regulation. 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. Conclusion NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.

Keywords

• Benign nerve sheath tumor
• NRG1
• PI3K/AKT
• M2 macrophage
• Neutrophil
• Biomarker