Comprehensive Analysis of Sterol O-Acyltransferase 1 as a Prognostic Biomarker and Its Association With Immune Infiltration in Glioma

Abstract

Metabolic reprogramming is a hallmark of glioma, and sterol O-acyltransferase 1 (SOAT1) is an essential target for metabolic therapy. However, the prognostic value of SOAT1 and its association with immune infiltration has not been fully elucidated. Using RNA-seq and clinical data of glioma patients from The Cancer Genome Atlas (TCGA), SOAT1 was found to be correlated with poor prognosis in glioma and the advanced malignancy of clinicopathological characteristics. Next, the correlation between SOAT1 expression and tumor-infiltrating immune cells was performed using the single-sample GSEA algorithm, gene expression profiling interactive analysis (GEPIA), and tumor immune estimation resource version 2 (TIMER2.0); it was found that SOAT1 expression was positively correlated with multiple tumor-infiltrating immune cells. To further verify these results, immunofluorescence was conducted on paraffin-embedded glioma specimens, and a positive trend of the correlation between SOAT1 expression and Treg infiltration was observed in this cohort. Finally, differentially expressed gene analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the biological processes and signaling pathways that SOAT1 may be involved in during glioma pathogenesis. A protein-protein interaction network was established, and co-expression analysis was conducted to investigate the regulatory mechanism of SOAT1 in glioma. To the best of our knowledge, this is the first comprehensive study reporting that SOAT1 may serve as a novel prognostic biomarker associated with immune infiltrates, providing a novel perspective for glioma metabolic therapy.

Identification of gene signatures and molecular mechanisms underlying the mutual exclusion between psoriasis and leprosy

“…SOAT1 was downregulation in psoriasis skin lesions 50 , The function SOAT1 in psoriasis and leprosy has not been extensively studied. SOAT1 expression level was positively correlated with macrophages, neutrophils, Th17 cells, and activated dendritic cells, while negatively correlated with plasmacytoid dendritic cells or natural killer cells in glioma 51 . Inhibition of SOAT1 expression can have anti-inflammatory effects by altering free cholesterol levels or oxysterol levels 52 .…”

Targeting sterol-O-acyltransferase 1 to disrupt cholesterol metabolism for cancer therapy

“…More importantly, SOAT1 expression was found to be positively correlated with multiple chemokine/chemokine receptor gene and various checkpoint genes, including PD-L1. These results indicated that SOAT1 overexpression may affect immune infiltration and tumor immune escape via increasing the secretion of chemokines and the levels of checkpoint genes ( 58 ). Nevertheless, both the mechanism by which SOAT1 promotes tumor growth and immune escape need to be further studied.…”

Crosstalk between cholesterol metabolism and psoriatic inflammation

“…ACAT1 can reduce cell proliferation and induce cell apoptosis ( 157 ). A bioinformatics study showed that the expression of ACAT1 was positively linked to macrophages, neutrophils, Th17 cells, and activated dendritic cells but negatively linked to plasmacytoid dendritic cells or natural killer cells ( 158 ). Inhibiting ACAT1 decreases the number of inflammatory monocytes and macrophages and changes them to an anti-inflammatory M2 phenotype, and blocking ACTA1 also decreases the expression of inflammatory factors like MCP-1 and CCL5/7 ( 159 ).…”