Constructing a Glioblastoma Prognostic Model Related to Fatty Acid Metabolism Using Machine Learning and Identifying...

Background: Increased fatty acid metabolism (FAM) is an important marker of tumor metabolism. However, the characterization and function of FAM-related genes in glioblastoma (GBM) have not been fully explored. Method: In the TCGA-GBM cohort, FAM-related genes were divided into three clusters (C1, C2, and C3), and the DEGs between the clusters and those in the normal group and GBM cohort were considered key genes. On the basis of 10 kinds of machine learning methods, we used 101 combinations of algorithms to construct prognostic models and obtain the best model. In addition, we also validated the model in the GSE43378, GSE83300, CGGA, and REMBRANDT datasets. We also conducted a multifaceted analysis of F13A1, which plays an important role in the best model. Results: C2, with the worst prognosis, may be associated with an immunosuppressive phenotype, which may be related to positive regulation of cell adhesion and lymphocyte-mediated immunity. Using multiple machine learning methods, we identified RSF as the best prognostic model. In the RSF model, F13A1 accounts for the most important contribution. F13A1 can support GBM malignant tumor cells by promoting fatty acid metabolism in GBM macrophages, leading to a poor prognosis for patients. This metabolic reprogramming not only enhances the survival and proliferation of macrophages, but also may promote the growth, invasion, and metastasis of GBM cells by secreting growth factors and cytokines. F13A1 is significantly correlated with immune-related molecules, including IL2RA, which may activate immunity, and IL10, which suggests immune suppression. F13A1 also interferes with immune cell recognition and killing of GBM cells by affecting MHC molecules. Conclusions: The prognostic model developed here helps us to further enhance our understanding of FAM in GBM and provides a compelling avenue for the clinical prediction of patient prognosis and treatment. We also identified F13A1 as a possibly novel tumor marker for GBM which can support GBM malignant tumor cells by promoting fatty acid metabolism in GBM macrophages.