Identifying SLC2A6 as the novel protective factor in breast cancer by TP53-related genes affecting M1 macrophage infiltration

AbstractThe high heterogeneity of breast cancer (BC) caused by pathogenic gene mutations poses a challenge to immunotherapy, but the underlying mechanism remains unknown. The difference in the infiltration of M1 macrophages induced byTP53 mutations has a significant impact on BC immunotherapy. The aim of this study was to develop aTP53-related M1 macrophage infiltration molecular typing risk signature in BC and evaluate the biological functions of the key gene to find new immunotherapy biomarkers. Weighted correlation network analysis (WGCNA) and negative matrix factorization (NMF) were used for distinguishing BC subtypes. The signature and the nomogram were both constructed and evaluated. Biological functions of the novel signature geneSLC2A6 were confirmed throughin vitro andin vivo experiments. RNA-Sequencing and protein profiling were used for detecting the possible mechanism ofSLC2A6. The results suggested that four BC subtypes were distinguished byTP53-related genes that affect M1 macrophage infiltration. The signature constructed by molecular typing characteristics could evaluate BC's clinical features and tumor microenvironment. The nomogram could accurately predict the prognosis. The signature geneSLC2A6 was found to have an abnormally low expression in tumor tissues. Overexpression ofSLC2A6 could inhibit proliferation, promote mitochondrial damage, and result in apoptosis of tumor cells. The HSP70 family member protein HSPA6 could bind with SLC2A6 and increase with ...
Source: Apoptosis - Category: Molecular Biology Source Type: research