Glycolysis-Related SLC2A1 Is a Potential Pan-Cancer Biomarker for Prognosis and Immunotherapy

SIMPLE SUMMARY: Enhanced glycolysis is a major feature of cancer glycometabolism, and SLC2A1 is one of the pivotal genes in cancer glycometabolism. Although SLC2A1 plays an important role in the growth of many cancers, pan-cancer analysis allows us to more comprehensively and systematically understand the function and role of SLC2A1 in cancers. In this study, we found that SLC2A1 was highly expressed in most cancers, and resulted in poor prognosis. M6A methylation might be one of the important factors for the high expression level of SLC2A1. SLC2A1 not only enhanced cancer glycolysis, but also affected the tumor microenvironment. Notably, SLC2A1 was significantly and positively correlated with the T-cell-exhaustion biomarkers PD-L1 and CTLA4. Collectively, SLC2A1 may provide new strategies for pan-cancer treatment, especially cancer immunotherapy. ABSTRACT: SLC2A1 plays a pivotal role in cancer glycometabolism. SLC2A1 has been proposed as a putative driver gene in various cancers. However, a pan-cancer analysis of SLC2A1 has not yet been performed. In this study, we explored the expression and prognosis of SLC2A1 in pan-cancer across multiple databases. We conducted genetic alteration, epigenetic, and functional enrichment analyses of SLC2A. We calculated the correlation between SLC2A1 and tumor microenvironment using the TCGA pan-cancer dataset. We observed high expression levels of SLC2A1 with poor prognosis in most cancers. The overall genetic alteration frequency of SLC2A1 was 1.8% in pan-cancer, and the SLC2A1 promoter was hypomethylation in several cancers. Most m6A-methylation-related genes positively correlated with the expression of SLC2A1 in 33 TCGA cancers. Moreover, SLC2A1 was mainly related to the functions including epithelial–mesenchymal transition, glycolysis, hypoxia, cell-cycle regulation, and DNA repair. Finally, SLC2A1 positively associated with neutrophils and cancer-associated fibroblasts in the tumor microenvironment of most cancers and significantly correlated with TMB and MSI in various cancers. Notably, SLC2A1 was remarkably positively correlated with PD-L1 and CTLA4 in most cancers. SLC2A1 might serve as an attractive pan-cancer biomarker for providing new insights into cancer therapeutics.