Vestibular schwannoma (VS), which originates from the Schwann cell sheath of the vestibular cochlear nerve, mostly occurs in the VIII pair of cranial nerves, about 80% of them occurred in vestibule(Babu et al. 2013). In addition to vestibular nerve damage such as hearing damage and vertigo, trigeminal nerve and facial nerve injury usually occur (Andersen et al. 2015), even hydrocephalus (di Russo et al. 2020), brain stem compression and other manifestations. At present, surgery and radiation are the main treatment, but the risks and sequelae of both will seriously affect the physical and mental health of patients in the long term, and there is no clear drug treatment plan(Kaul and Cosetti 2018; Starnoni et al. 2020). Therefore, the research on molecular targeted therapy of VS is needed.
In this study, we identified 226 up-regulated DEGs and 148 down-regulated DEGs between VS and normal tissues. These are mostly related to GO-CC, mainly concentrated outside the cell membrane and related to the cell adhesion function. KEGG pathway has enriched Cell adhesion molecules, MicroRNAs in cancer and Focal adhesion pathways, Ras signaling pathway and PI3K-Akt signaling pathway. The Ras and PI3K/Akt/mTOR pathways are involved in the pathogenesis of vestibular schwannoma according to research(Breun et al. 2018). The first ten core genes were selected by PPI, including EGFR, PPARG, CD86, CSF1R, SPP1, CDH2, CCND1, CAV1, CYBB and NCAM1. Except for EGFR, PPARG and CAV1, all the others were up regulated in VS. Abnormal expression of these genes is related to poor prognosis of vestibular schwannoma.
We detected these 10 central genes related to VS. EGFR, which has been shown to be related to NF2 gene, is involved in Ras/RAF pathway (Fong et al. 2011). Studies have shown that osteopontin gene is up-regulated, it indicates SPP1 may play a key role in VS(Torres-Martin et al. 2013). CCND1, as a cyclin D1, was overexpressed in vestibular schwannoma (68%)(Jabbour et al. 2016). Down-regulation of CAV1 has also been revealed as a new candidate gene in vestibular schwannoma(Aarhus et al. 2010). Overexpression of above genes is markedly associated with adverse clinical outcomes of VS, and our results are consistent with other studies. However, in current studies, PPARG mainly acts on the adipogenesis pathway (Pan et al. 2020). CD86 is involved in immune response as a proinflammatory cytokine(Chang et al. 2020). Colony stimulating factor 1 receptor (CSF1R) can cause associated leukoencephalopathy(Zhan et al. 2020) and neuroprotective effect of microglia cell depletion involved in PD and AD(Crapser et al. 2020; Oh et al. 2020). PPARG, CD86 and CSF1R were all involved in the proinflammatory process(Bancells et al. 2010). In addition, CDH2 up-regulation promotes epithelial-mesenchymal transformation (EMT), which is involved in the pathogenesis of various cancers (Wang et al. 2020). In addition to being more common in chronic granulomas (Yu and Yang 2020), CYBB is also common in the protection of autoimmune neuroinflammation (Keller et al. 2020). Neural cell adhesion molecule 1 (NCAM-1) has been implicated in several biological processes related to the brain(Vukojevic and Mastrandreas 2020). These six genes are mainly related to neuroinflammation and cell adhesion. Although these genes's role is not clear in VS, it still has the significance and value of further research.
In addition to surgery, we also need to further choose effective drug treatments to delay growth, and whice is more conducive to reducing disability and deterioration. At the same time, it can reduce the impact on physical and mental health. Therefore, the study of new targeted drugs is of great significance. In this article, we further analyzed drugs targeting ten core genes based on gene-drug interactions. Finally, afatinib and osimini are proposed as potential therapeutic drugs.