Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and...

Lipid metabolism is crucial to tumor growth and immune microenvironment as well as drug sensitivity in glioma. Identifying prognostic indicators of glioma and elucidating the mechanisms of glioma progression are critical for improving the prognosis of glioma patients. In this study, we investigated the role and prognostic value of metabolism-related genes in glioma by integrative analysis of datasets from GEO, CGGA, and TCGA. Based on clinical data and transcriptome data, we found that the expression pattern of three major pathways related to lipid metabolism is fatty acid^high-phospholipid^high-triglyceride^low, which is associated with better prognosis and immune infiltration. The genes involved in these three pathways were used to generate a prognostic model, which showed high stability and efficiency in the test set and validation set. The spatial transcriptome of glioma patients revealed that the microenvironment of the regions with high expression of risk genes CAV1 and SCD is in a state of hypoxia, EMT, and cell cycle arrest, and thus can be used as markers of metabolic reprogramming in the tumor microenvironment. In the high-risk group, M0 macrophages and M1 macrophages were significantly enriched, and the risk score was significantly correlated with gene mutation and methylation of risk genes. We further performed drug sensitivity screening corresponding to different risk genes. This study provided novel insights into the differential immune microenvironment with different expression patterns of metablism-related genes and highlighted the spatial and temporal synergy of tumor progression and metabolic reprogramming.