A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis

Metabolic reprogramming is a significant factor that regulates the function and differentiation of immune cells, thereby influencing the progress of the immune response. The intricate interplay between glutamine metabolism and the immune microenvironment (TME) plays crucial roles in the pathogenesis of cancer. The initiation of glutamine metabolism is facilitated by the enzyme GLS1; however, its oncogenic role remains unclear.

In this pancancer analysis, we aimed to investigate the potential oncogenic mechanism of GLS1 across various tumor types in The Cancer Genome Atlas (TCGA) dataset.

Our results revealed variable expression levels of GLS1 across different cancer types. Notably, higher expression levels of GLS1 were associated with worse prognosis in patients with kidney renal papillary cell carcinoma (KIRP, HR = 1.01; p < 0.01), liver hepatocellular carcinoma (LIHC, HR = 1.02; p < 0.01), and mesothelioma (MESO, HR = 1.01; p < 0.01). Additionally, we observed distinct associations between GLS1 expression levels and tumor methylation levels, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration (IFL), and immune scores in several tumor types. We also detected the enrichment of GLS1 in key pathways, such as the mTOR, JAK, and KRAS pathways. Furthermore, we observed associations between GLS1 expression levels and a wide range of immune checkpoint genes, including both immunoinhibitors and immunostimulators, in most tumors.

Our study provides initial insights into the oncogenic roles of GLS1 across different tumors. These findings suggest that GLS1 can serve as a potential biomarker for determining prognosis and designing therapeutic strategies for various tumor types.