Purpose: Selenophosphate synthetase 2 (SEPHS2) has been shown to regulate selenoprotein biosynthesis by catalyzing the synthesis of active selenium donor selenophosphate. SEPHS2  influences the survival of tumor cells. However, few studies have explored the expression level and prognostic of SEPHS2  in various cancers.
Methods: The expression of SEPHS2  in human tumor tissues and normal adjacent tissues was analyzed in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN databases. Cox regression analysis and Kaplan–Meier curve analysis were performed to analyze the association of SEPHS2  expression with the prognosis of cancer patients. The expression and prognosis of SEPHS2  in gliomas were further verified using the Chinese Glioma Genome Atlas (CGGA) dataset. The relationship between SEPHS2  and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens was comprehensively explored using a TCGA cohort. The mechanism by which SEPHS2  regulates tumor progression was explored by using the STRING database. A nomogram was constructed using the R software to predict the overall survival (OS) of patients with brain lower grade glioma (LGG).
Results: SEPHS2  was highly expressed in many cancers including LGG. Its high expression was significantly associated with poor OS, disease-free survival (DFS), and progression-free survival (PFS). Univariate and multivariate Cox analyses showed that SEPHS2  was an independent prognostic factor for LGG. Concordance index and calibration curves revealed that the nomogram had good predictive performance (concordance index: 0.791; 95% CI: 0.732– 1). A significant correlation was found between SEPHS2  and immune infiltration, TMB, MSI, and tumor neoantigens across diverse cancers. Enrichment analysis showed that SEPHS2  may regulate the PPAR signaling pathway.
Conclusion: SEPHS2  expression regulates tumor development and it is a potential treatment target and prognostic biomarker, especially for lower grade glioma.
Keywords: SEPHS2 , selenoprotein, cancer, prognosis, biomarker