Bioinformatics exploration of SPHKAP's role in IDH-mutant glioma involving energy metabolism, prognosis, and immune modulation.

Background: The current understanding of glioma pathogenesis is limited by the lack of comprehensive insights into the metabolic reprogramming associated with isocitrate dehydrogenase (IDH) mutations. This study aims to contribute a step to this gap by investigating the role of energy metabolism-related genes in glioma. Our objective is to identify key molecular markers that could serve as prognostic markers and potential therapeutic targets for more effective treatment strategies in IDH-mutant glioma patients.

Methods: We conducted an in-depth analysis of gene expression data from TCGA, CGGA, and GEO databases, employing Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis to pinpoint candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to elucidate the biological pathways implicated by these genes. Protein-Protein Interaction (PPI) and Gene Multiple Association Network Integration Algorithm (GeneMANIA) networks were constructed to map gene interactions, and survival analysis and Cox regression models were utilized to assess the prognostic value of the identified genes. Additionally, CIBERSORT was used to evaluate immune cell infiltration in the tumor microenvironment.

Results: Our findings identified SPHKAP as a gene significantly downregulated in glioma tissues compared to control samples. Specifically, low SPHKAP expression was associated with a poorer prognosis of patients with IDH-mutant glioma and linked to the expression of key enzymes involved in energy metabolism. Meanwhile, in IDH-mutant gliomas, reduced SPHKAP expression was correlated with increased macrophage infiltration, enhanced T cell response, and upregulation of immune checkpoint genes, highlighting its role as an independent prognostic marker.

Conclusion: This study reveals the differential expression of SPHKAP in glioma, suggesting its potential as a prognostic marker for IDH-mutant gliomas, providing information for future studies aimed at developing targeted therapies for glioma patients.