CYTH4 Is A Potential Biomarker Associated With Immune Cell Infiltration In Glioblastoma

Objective: Glioblastoma(GBM)is the most common and aggressive primary malignant tumor of the central nervous system,with the highest mortality rate among all gliomas.GBM is classified as a grade IV astrocytoma by the World Health Organization(WHO)and has a poor prognosis.Although standard treatment regimens include surgical resection,radiation therapy,and adjuvant chemotherapy with temozolomide(TMZ),GBM still poses a significant threat to the patient’s life.Immune cells in the tumor microenvironment play an important role in the formation of the immunosuppressive tumor microenvironment in GBM.It is crucial to explore new prognostic features related to tumor immune infiltration and elucidate the molecular mechanisms of astrocytoma to improve the accuracy of prognosis for GBM patients and develop more effective treatment strategies in the field of GBM treatment.Members of the cytohesin family have been shown to serve as prognostic markers for tumors and are widely involved in tumor progression.It is highly necessary to fully evaluate the correlation between cytohesin family members and GBM.Methods: Based on multiple public databases such as CGGA,TCGA,GEO,HPA and online websites such as UCSC and GEPIA,this study comprehensively and fully evaluated the expression level and prognostic value of cytohesin members in glioma.Univariate and multivariate Cox regression analysis displayed three variables including age,WHO grade and CYTH4 expression were independent prognostic factors for glioma.Based on this,a prediction model was constructed and subsequently verified by concordance index(C-Index)and calibration curve.After selecting CYTH4 as the target gene for further research,the expression and prognostic value of CYTH4 in GBM were further validated by using multiple datasets and clinical specimens collected.The correlation between the expression level of CYTH4 and specific genomic alterations in GBM has been analyzed and confirmed.Correlation between CYTH4 and immune cell infiltration abundance and immunolabeled molecules in GBM was fully evaluated by using single-sample gene set enrichment analysis(ss GSEA),ESTIMATE,TIMER and TISIDB website.Relationship between CYTH4 and cytolytic activity(CYT)score and T cell inflammatory gene expression profile(GEP)was also confirmed.The "Cluster Profiler" R package and GSEA software were used to explore potential pathways for CYTH4 to play a role in GBM.Cell function experiment further confirmed the role of CYTH4 in GBM.Results: Cytohesin members had different expression levels between glioma and normal samples.The expression level of CYTH4 tends to increase with grade.CYTH4 expression together with the two variables of age and WHO grade were independent prognostic factors for glioma.Prediction model constructed based on the three variables has favorable accuracy and applicability.The significantly elevated expression of CYTH4 in GBM has been confirmed by multiple databases and clinical samples,and also predicts a poor prognosis for GBM.Copy number variations(CNVs)and somatic mutationsof in GBM samples showed a correlation with CYTH4 expression.In addition,CYTH4 was significantly associated with immune infiltration and immune-related markers in GBM.Functional enrichment analysis further suggested that CYTH4 was involved in the GBM immune process,and was also related to cell migration,JAK/STAT pathway and toll-like signaling pathway.Cell function experiments further confirmed that CYTH4 is involved in tumor cell migration of GBM.Conclusion:1 CYTH4 expression may be upregulated in glioma,especially GBM,and predicts poor prognosis.2 CYTH4 may have a potential link to GBM genomic alterations.3 CYTH4 may be significantly correlated with tumor immune infiltration of GBM.4 CYTH4 may affect GBM progression through mechanisms such as cell adhesion and JAK/STAT pathway.5 Silencing CYTH4 can inhibited tumor cell migration of GBM.