Abundant expression of ferroptosis-related SAT1 is related to unfavorable outcome and immune cell infiltration in low-grade glioma

Abstract

Abstract Background Low-grade glioma (LGG) is susceptible to ferroptosis, which is involved in TMZ resistance. Ferroptosis induction can enhance the sensitivity to TMZ and synergistically kill glioma cells. T cell-promoted tumor ferroptosis is a vital anti-tumor mechanism of immune checkpoint inhibitors. The SAT1 activation is closely related to ferroptosis upon ROS induction due to the upregulation of arachidonate 15-lipoxygenase (ALOX15) expression. Methods The expression of SAT1 in pan-cancer and corresponding normal tissue from the TCGA data portal was primarily explored. The landscape of SAT1 and immune cell infiltration and their corresponding gene marker sets in different tissues were further explored. Additionally, we evaluated the relationships between SAT1 and the clinicopathologic parameters of LGG, and the disease-specific survival (DSS), progression-free interval (PFI), and overall survival (OS) were also assessed using KM survival curves and multivariate analysis in LGG. Meanwhile, the Gene Set Enrichment Analysis (GSEA) was also implemented to determine the potential effect of the SAT1 gene in LGG. Furthermore, the predictive power of SAT1 was validated using an independent LGG cohort from the Chinese Glioma Genome Atlas (CGGA) data. Results In general, the expression of SAT1 is different between most tumors and their adjacent normal tissues. The results demonstrated that SAT1 expression is positively associated with TMB in LGG, BRCA, and THYM. The results displayed that the expression level of SAT1 is obviously correlated with the level of infiltrating macrophages and CD8 + T cells, and the levels of most immune gene sets were associated with the SAT1 expression in LGG. Interestingly, univariate and multivariate models significantly indicated that the OS and PFI of patients with LGG with high SAT1 levels were poorer than those with low SAT1 expression in the TCGA LGG cohort. GSEA showed that SAT1 was involved in immune regulation and multiple signaling pathways. Finally, our analysis demonstrated that SAT1 was closely associated with IDH mutation, 1p19q codeletion, chemoradiotherapy resistance and disease recurrence. Conclusions Abundant expression of SAT1 was related to poor disease prognosis and abundant immune cell infiltration in LGG.

Keywords

• Ferroptosis
• SAT1
• Low-grade glioma
• Pan-cancer
• Immune cells
• Immune checkpoint