Bioinformatics Analyses Reveal the Prognostic Value and Biological Roles of SEPHS2 in Various Cancers

Abstract

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.

Pharmacogenomic Analysis of Combined Therapies against Glioblastoma Based on Cell Markers from Single-Cell Sequencing

“…The current GBM prognosis is abysmal, with a median survival time of 12-15 months under standard treatments [24]. Recent evidence from clinical trials showed that targeted therapy does not improve the prognosis of patients with GBM [25]. TMB has been reported to influence immunotherapeutic effectiveness across tumor types and can be used to predict the survival of diverse tumors with CTLA-4 or anti-PD-1 treatments [26].…”

Current Understanding of Human Polymorphism in Selenoprotein Genes: A Review of Its Significance as a Risk Biomarker

“…In mammals, the role of SEPHS2 is to provide the active Se donor, and SPS1 does not have a clear function established, but it could have a non-essential role in selenoprotein metabolism [204]. SEPHS2 is related to the aggressiveness and malignant tumor grade [205,206]. Its expression is related to immune infiltration, and it could act in the development of tumors through the peroxisome proliferator-activated receptors signaling pathway [205].…”

“…SEPHS2 is related to the aggressiveness and malignant tumor grade [205,206]. Its expression is related to immune infiltration, and it could act in the development of tumors through the peroxisome proliferator-activated receptors signaling pathway [205].…”

Selenoprotein GPX1 is a prognostic and chemotherapy-related biomarker for brain lower grade glioma

“…Se supplementation has been shown to lessen the occurrence and severity of carcinogenesis in the liver, esophagus, pancreas, prostate, colon, and mammary glands [11]. In patients with glioblastoma, se therapy reduced tumor severity and relieving disease manifestations [12]. The antioxidant enzyme GPX1, was the rst discovered mammalian selenoprotein in GPXs, which is commonly found in cell mitochondria and cytoplasm, has been linked to tumor spread and transformation in tumor cells [13,14].…”