Lipid metabolism as a marker for glioma aggressiveness.

Glioblastoma (GBM) is the most aggressive type of central system nervous tumor. There have been advances in glioma biology understanding, however, the current therapies are still inefficient. Additionally, new molecular markers are being explored for glioma grading, offering potential for novel diagnostic and drug targets. Considering the important role of lipid metabolism in tumorigenesis, understanding the lipid-related pathways in glioma could lead to new important markers. Here, lipid metabolism was analyzed by integrating two different data sources, the transcriptome data from The Cancer Genome Atlas (TCGA), and experimental data from tumor cells; to investigate how lipid metabolism is regulated in glioma. We compared the expression of 743 lipid-related genes in public RNAseq data of glioma patients (n=681) to lipidomic analyses of glioblastoma cell lines (A172, U87MG, and T98G). We identified 29 lipid-related genes correlated to prognosis and constructed a risk-signature based on these genes. Extracellular matrix related genes were positively correlated to the risk score. Our findings revealed that aggressiveness is linked to alterations in membrane composition, characterized by an increase in phospholipids, coupled with a decrease in cholesterol and fatty acid unsaturation levels, which impact membrane physical properties. Modulation of critical signaling lipids, specifically sphingolipids, was also observed. Here, we identify lipid markers that may play a significant role in glioma. The converging axis involving sphingomyelinase and sphingosine-1-phosphate, mediated by the actions of sphingomyelinase SMPD1 and sphingosine-kinase SPHK1, emerged as a pivotal factor in glioma. This study suggests that lipid membrane composition is pivotal for the GBM aggressiveness.