Jinlu Gan,1,* Yanling Zhang,2,* Deqiang Lei,1 Yingchun Zhou,1 Hongyang Zhao,1 Lei Wang1 

1Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lei Wang, Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Email leiwang_ns@hust.edu.cn; leiwang_ns@hotmail.com Hongyang Zhao, Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Email hyzhao750@sina.com

Background: Vestibular schwannomas (VSs) exhibit a range of tumor behaviors, such as growth patterns and auditory dysfunction. Recent research has offered insights into the inflammatory microenvironment in modulating tumor dynamics. This study investigates the role of inflammatory genes and immune infiltration in VS pathogenesis.
Methods: We retrieved mRNA microarray data of VSs and normal nerves from the GEO database (GSE141801, GSE108524, and GSE56597), focusing on bioinformatic analysis of inflammatory response genes. Based on the evidence provided by bioinformatics analysis, we assessed the expression levels of Iba-1, IL-10, IL-10RA, and IL-18 in 31 VS patients via immunohistochemistry and delved into their association with tumor size and auditory dysfunction.
Results: We identified 1117 differentially expressed genes (DEGs) in VSs compared to normal nerves, showing an upregulation in inflammatory pathways. Intersection with inflammatory response genes (IRG) yielded 41 significant IRG-DEGs. Network analysis identified a core module of 10 IRG-DEGs and 11 hub genes, most of which were inflammatory cytokines. Immune infiltration analysis showed macrophage activation and M2 polarization. These findings were validated in an independent dataset (GSE39645). To further explore the association between inflammation and tumor behaviors, immunohistochemistry analysis was conducted on VS samples and the results exhibited notable associations between the macrophage marker (Iba1) and inflammatory cytokines (IL-10, IL-10RA, and IL-18) with both tumor size and auditory dysfunction. In particular, the multiple regression analysis of inflammatory cytokines demonstrated that IL-10 and IL-10RA were statistically significant predictors of tumor size, while IL-18 was associated with hearing loss.
Conclusion: Our study underscores the role of inflammation in VS pathogenesis, showing that macrophage activation with M2 polarization and the expression of inflammatory cytokines, especially IL-10/IL-10RA and IL-18, are linked to tumor size and auditory function. This study highlights the inflammatory landscape’s impact on VS behaviors, providing a basis for targeted therapeutic strategies.

Keywords: vestibular schwannomas, inflammatory response, macrophages, immune infiltration, auditory dysfunction, tumor size