Bioinformatics analysis of SH2D4A in Glioblastoma Multiforme to evaluate immune features and predict prognosis

Abstract

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The predictive role of SH2D4A has been shown to be closely related to various cancers progression,but there is no comprehensive analysis of the clinical significance in glioblastoma. Hence, this study aimed to explore the relationship between the prognosis of GBM and SH2D4A expression. Methods: The expression of SH2D4A in GBM was analyzed using TIMER2.0 and GEPIA, and validated by qRT-PCR experiments. The CGGA database analyzed the differential expression of SH2D4A in glioma and evaluated the impact of SH2D4A on the survival of glioma patients.LinkedOmics database and GeneMANIA database were studied for SH2D4A co-expression network. A lasso regression model and nomogram were constructed to assess the prognosis of GBM. TCGA database was used to do a GSEA to find functional differences. The relationship between SH2D4A expression and tumor-infiltrating immune cells was analyzed using xCELL, the CIBERSORT algorithm and the TIMER database. Results: In GBM patients, we found that the expression of SH2D4A was upregulated, and the elevated expression of SH2D4A was strongly associated with the grade of the tumor. High SH2D4A expression was found to be a significant independent predictor of poor overall survival (OS) in GBM patients by survival curve analysis and multivariate cox regression analysis. GSEA revealed that SH2D4A was mainly enriched in extracellular matrix tissues, and the expression level of SH2D4A was inversely correlated with the level of infiltration of CD8+T cells, CD4+T cells, B cells, neutrophils and macrophages in GBM, but was positively correlated with the level of dendritic cell infiltration. Immunoassays suggest that altered SH2D4A expression may affect the immune infiltration of GBM tissues and thus affect the survival outcome of GBM. Conclusion: In addition to being a possible prognostic marker and therapeutic target for GBM, SH2D4A may also accelerate the progression of GBM.