The pan-cancer landscape of glutamate and glutamine metabolism: A comprehensive bioinformatic analysis across 32 solid cancer types.

Glutamine metabolism is a hallmark of cancer metabolism, which matters in the progression of the tumor. This synthetic study conducted a large-scale systematic analysis at the pan-cancer level on the glutamate and glutamine metabolism (GGM) across 32 solid tumors from the TCGA database. The glutamine metabolism activity was quantified through a scoring system. This study revealed that the GGM score in tumor tissues was up-regulated in 13 cancer types (BCLA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PAAD, PRAD, READ, STAD, THYM, UCEC) and down-regulated in 4 cancer types (CHOL, GBM, LIHC, THCA), exhibiting tissue specificity. The mRNA expression levels of glutamine metabolism-related genes were relatively high, and GLUL exhibited the highest expression level. The expression levels were up-regulated with copy number amplification. ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in protein levels in cancer tissues compared to normal tissues, making them potential pan-cancer therapeutic targets. For the TME related to glutamine metabolism, the GGM score exhibited significant immune and stromal environment inhibitory effects in all involved tumors. Up-regulated GGM score indicated the widespread promotion of drug resistance at the pan-cancer level. GGM score and glutamine metabolism-related genes signature tended to be risk factors for the overall survival of cancer patients. [Display omitted] • The Glutamate and glutamine metabolism (GGM) score and the nine-gene GGM-related signature serve as prognostic markers in various cancer types. • ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in both mRNA and protein levels, making them potential pan-cancer therapeutic targets. • The GGM score exhibits significant associations with genomic Copy Number Variations, Single Nucleotide Variations, DNA methylation, and decreased drug sensitivity. • GGM score is generally positively correlated with TAM M2, MDSC, and Immune Exclusion. • GGM-related molecular subtyping is intricately linked to patient prognosis and drug sensitivity on a pan-cancer scale. [ABSTRACT FROM AUTHOR]