Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma

Abstract

Cuproptosis is a newly discovered form of cell death. It is regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus (GEO) and quantitative real-time polymerase chain reaction (qPCR). The Human Protein Atlas (HPA) and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to validate our results at the protein level. Multivariable analysis and Kaplan–Meier survival curves were used to examine the relationship among SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource (TIMER) databases. Small interfering RNA was used to knock down the SLC31A1 expression, and the cell proliferation, apoptosis, and migration were analyzed using cell counting kit-8, flow cytometry, and transwell. The glioma patients have higher SLC31A1 expression levels, which increase as the World Health Organization (WHO) grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The immune infiltration analysis shows the SLC31A1 gene positively correlates with T helper 2 (Th2) cells, macrophages, and M2-type macrophages and negatively correlates with plasmacytoid dendritic cells (pDCs), natural killer (NK) CD56bright cells, and CD8 T cells. The in vitro KD experiment shows the SLC31A1 knockdown depressed the glioma cell proliferation and migration and promoted the apoptosis rate. The SLC31A1 gene expression can shorten the survival time of glioma patients. In vitro study shows that SLC31A1 can promote cell proliferation, and migration, and depress the cell apoptosis of glioma cells. It also can promote the formation of a tumor-suppressive microenvironment.