Patients with lower-grade gliomas (LGGs) have highly diverse clinical outcomes. Although histological features and molecular markers have been used to predict prognosis, the identification of new biomarkers for the accurate prediction of patient outcomes is still needed. The serine synthesis pathway (SSP) is important in cancer metabolism. There are three key regulators, including phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), and phosphoserine aminotransferase 1 (PSAT1), in SSP. However, their clinical importance in LGGs is still unknown. In this study, we used the bioinformatics tool in the Gene Expression Profiling Interactive Analysis (GEPIA) website to examine the prognostic significance of PHGDH, PSPH, and PSAT1 genes in LGGs. PSAT1 gene expression was then identified as a potential biomarker candidate for LGGs. Datasets from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were further used to explore the prognostic role of PSAT1 gene. Our results demonstrated that PSAT1 overexpression is a favorable prognostic marker of LGGs and significantly correlated with patient age ≤40, and a lower WHO histological grade, as well as mutations in IDH1, TP53 and ATRX, but not with chromosome 1p19q codeletions. More importantly, LGG patients with isocitrate dehydrogenase 1 (IDH1) mutations, chromosome 1p19q codeletions, and PSAT1 overexpression may have the best overall survival (five-year survival rate: 100%). Finally, we observed a coordinated biological reaction between IDH1 mutations and PSAT1 overexpression, and suggested overexpression of PSAT1 might enhance the function of mutant IDH1 to promote a favorable outcome in LGG patients. In conclusion, our study confirmed the importance of identifying the overexpression of PSAT1 as a favorable prognostic marker of LGGs, which may compensate for the limitation of IDH1 mutations and chromosome 1p19q codeletion in the prognostication of LGGs.

Glioblastoma (GBM) is a typical brain tumor with survival below ten percent at 5 years after diagnosis. The genetic alternation and histological features are integrated into the classification of gliomas for better clinical management of GBM. However, the development of therapeutic strategies and diagnosis for GBM patients remains poor. In this study, we found that downregulation of phosphoserine aminotransferase (PSAT1) mediated tumorigenesis of GBM. Analyses of available clinical datasets showed that PSAT1 downregulation was associated with poor survival of GBM patients. In western‐blot analysis of our GBM cell panel, PSAT1 protein was shown to be overexpressed in U87 and SNB75 cells, but downregulated in T98G and G9t cells. We overexpressed PSAT1 in T98G and G9T cells and knocked down PSAT1 in U87 and SNB75 cells for further study. The colony formation assay showed that PSAT1 overexpression inhibited clonal expansion in T98G and G9T cells. PSAT1 knockdown promoted cell growth in U87 and SNB75 cells. Furthermore, PSAT1 knocked‐down cells revealed significant tumorigenesis in mouse xenograft tumor model. The microarray assay indicated that downregulation of PSAT1 plays an important role in GBM tumorigenesis.