Molecular analysis of spinal nerve sheath tumors has identified CSH1 as a candidate gene for differentiating between Schwannomatosis and Spinal schwannoma

Purpose The most common form of schwannomatosis is characterized by multiple and recurrent spinal schwannomas, exhibiting symptoms similar to those of spinal schwannomas. The molecular factors responsible for tumor multiplicity in schwannomatosis are not yet understood. This study aims to identify differentially expressed genes (DEGs) between intradural spinal schwannomas and schwannomatosis, and explore the underlying mechanisms of schwannomatosis pathogenesis Methods We used high-throughput sequencing technology to sequence 30 tumor samples(15 conventional spinal schwannomas and 15 schwannomatosis cases), and identified DEGs between the two sample groups using the limma R package. Using machine learning algorithms to identify more significant biomarkers from the DEGs.We evaluated the diagnostic value of these biomarkers for schwannomatosis using receiver operating characteristic (ROC) curve analysis and an Alignment Diagram. Gene set enrichment analysis (GSEA) was employed to explore relevant pathways. Result Our findings revealed 249 DEGs, with OXTR, CSH1, SNCAIP, and DPP4 emerging as candidate genes.Subsequent q-PCR experiments validated these biomarkers' reliability. Validation showed that CSH1 expression was elevated in schwannomatosis samples, while DPP4, OXTR, and SNCAIP expressions were decreased compared to solitary schwannoma cells. ROC curves and the Alignment Diagram confirmed the stability and accuracy of our diagnostic model.GO functional annotation and KEGG pathway enrichment analysis indicated that these DEGs might be involved in biological activities related to immunity, inflammation regulation, and tumorigenesis. Conclusion We have developed a novel diagnostic model for distinguishing between schwannomatosis and spinal schwannomas. Moreover,These transcriptional changes enhance our understanding of the pathogenesis of schwannomatosis, identify risk factors, and provide insights into new therapeutic targets.