An integrated pan-cancer analysis of PSAT1: A potential biomarker for survival and immunotherapy

Abstract

Phosphoserine aminotransferase 1 (PSAT1) may be an oncogene that plays an important role in various cancer types. However, there are still many gaps in the expression of PSAT1 gene and its biological impact in different types of tumors. Here, we performed an integrated pan-cancer analysis to explore the potential molecular mechanisms of PSAT1 in cancers. We found that most human tumors express higher levels of PSAT1 than normal tissues, and that higher PSAT1 expression is associated with worse prognosis in Lung adenocarcinoma (LUAD), Pan-kidney cohort (KIPAN) and breast invasive carcinoma (BRCA), etc. In BRCA cases, the prognosis of patients with altered PSAT1 was worse than that of patients without alteration. In addition, PSAT1 hypermethylation is associated with T cell dysfunction and shortened survival time in BRCA. The Gene Set Enrichment Analysis (GSEA) analysis showed that PSAT1 can be enriched into the classic signaling pathways of cancer such as mTORC1 signaling, MYC targets and JAK STAT3. Further analysis demonstrated that PSAT1 was enriched in immune related signaling pathways in LUAD and BRCA. The results of immunoassay showed that PSAT1 was associated with immune cell infiltration in multiple cancer species. Furthermore, expression of PSAT1 was correlated with both tumor mutational burden (TMB) and microsatellite instability (MSI) in BRCA. Additionally, a remarkable correlation was found between PSAT1 expression and TMB in LUAD, and the expression of PSAT1 was negatively correlated with the Tumor Immune Dysfunction and Exclusion (TIDE) value, suggesting a good effect of immunotherapy. Together, these data suggest that PSAT1 expression is associated with the clinical prognosis, DNA methylation, gene mutations, and immune cell infiltration, contributing to clarify the role of PSAT1 in tumorigenesis from a variety of perspectives. What’s more, PSAT1 may be a new biomarker for survival and predicting the efficacy of immunotherapy for LUAD and BRCA.