| Background and AimsAs the most common primary tumor in the adult brain and spinal cord,glioma has been characterized by easy recurrence and poor prognosis.Despite the application of novel therapies such as immunotherapy and biologically targeted therapy,patient survival remains unsatisfactory.Therefore,it is crucial to study the intrinsic pathogenesis of glioma and explore novel targets that can affect patient prognosis.Voltage-gated sodium channels(VGSCs)are transmembrane macromolecular protein complexes that are classified into nine isoforms based on their alpha subunits.Their function is mainly to mediate Na?inward flow involved in action potential formation.NaV1.3,a subtype of VGSCs mainly expressed in the central nervous system,has been shown to be involved in regulating the malignant biological behavior of various tumors,but its role in glioma has not been reported in the literature.In this study,we aimed to explore the expression,role of NaV1.3 and the relationship between its expression and patient prognosis in glioma,analyze the functions and pathways involved in the regulation of NaV1.3 in glioma,construct a protein-protein interaction network(PPI),screen key genes by PPI to establish a NaV1.3-derived prognostic model,then conduct a comprehensive evaluation and validation of the model,and provides ideas for further research in the future.Methods1.The expression level of NaV1.3 in glioma was calculated by TCGA database,and the correlation between the expression level of NaV1.3 and the prognosis of glioma patients was analyzed by K-M curves and one-way/multi-factor COX regression.2.Real-time Quantitative PCR was used to detect the expression levels of NaV1.3 in glioma cell lines versus normal glial cell lines and paired clinical samples in glioma and paraneoplastic tissues.3.Patients were divided into high/low NaV1.3 expression groups according to the median expression level of NaV1.3,and NaV1.3-derived genes were screened for GO(functional)and KEGG(pathway)enrichment analysis using differential analysis,and the associated key protein-protein interaction network(PPI)was established.4.Key genes among NaV1.3-derived PPI were screened by Lasso regression and used to construct risk prediction prognostic models.5.The NaV1.3-derived prognostic model was comprehensively evaluated in terms of prognostic efficacy and relevant biological properties.Results1.NaV1.3 was significantly more highly expressed in gliomas in the pan-cancer analysis;compared with normal tissue,NaV1.3 was highly expressed in low-grade gliomas(LGG)and glioblastomas(GBM),and the difference was particularly significant in lowgrade gliomas.2.The expression level of NaV1.3 was significantly correlated with the prognosis of glioma patients and was an independent factor affecting the prognosis of patients;the expression level of NaV1.3 could determine the prognosis of glioma patients to a certain extent by measuring the expression level of NaV1.3.3.After GO annotation,NaV1.3-derived genes in gliomas are highly associated with functions such as inflammatory response,immune response,and cell adhesion mainly in tumors.In addition,NaV1.3-derived genes have significant interactions with pathways such as cytokine-cytokine receptor interaction pathway,PI3K-Akt signaling pathway,and IL-17 signaling pathway.4.The NaV1.3-derived prognostic model has good prognostic efficacy,and the prognosis of glioma patients can be determined relatively accurately based on the risk score.At the same time,there were significant differences in immune response,chemotactic properties,cell migration,and immune cell infiltration landscape between the high and low risk groups of patients in the model.5.RT-PCR was used to confirm that NaV1.3 expression was significantly higher in glioma samples than in paired paraneoplastic tissues;and NaV1.3 expression was significantly higher in glioma cell lines compared to normal glial cell lines.ConclusionThrough our study,we found that NaV1.3 showed high expression in gliomas and its expression level was significantly correlated with the prognosis of glioma patients.The NaV1.3-derived genes obtained after differential analysis were functionally enriched in inflammatory response,immune response,and cell adhesion,and significantly associated with cytokine-cytokine receptor interaction pathway,PI3K-Akt signaling pathway,and IL-17 signaling pathway in pathways;this study explored the expression,role,and Prognostic value of NaV1.3 in gliomas.We also constructed a NaV1.3-derived prognostic model with good prognostic performance using NaV1.3-derived genes,and confirmed the differences in immune response,chemotactic properties,cell migration,and immune cell infiltration landscape between patients in the high-risk group and those in the low-risk group. |
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